??????????? ?????? ?????? - ????????? ??????? ???????????? ? ????????????? (????????????? ?????)

????????? ??????? ???????????? ? ????????????? (????????????? ?????)
?.?. ????????., ????????????? ?.?., ???????? ?.?.

Cell therapy of dislipidemia and atherosclerosis. The paper reviews about cell transplantation as an alternative method of pathogenetic treatment of dislipidemia and atherosclerosis. At experimental modeling of atherosclerosis it was found out the possibility to decrease serum lipid concentration and to reduce aorta lipid infiltration by transplantation of donor hepatocytes, gene-modified hepatocytes and bone marrow cells. The first clinical results or human fetal hepatic cell transplantation for treatment of ischemic heart disease and gene-modified hepatocytes for treatment of familia hypercholesterolemia are presented.

???????? ?????? ? ????????? ?????????????? ??? ?????????????? ?????? ????????????????? ??????? ???????????? ? ?????????????. ?? ????????????????? ??????? ????????????? ???? ???????? ??????????? ???????? ???????????? ??????? ????????? ? ???????? ??????? ???????????? ????? ??? ?????????????? ????????? ???????????, ???-???????????????? ??????????? ? ?????? ???????? ?????. ???????????? ?????? ??????????? ?????????? ?????????????? ????????? ?????? ?????? ???????? ??? ??????? ??????????? ??????? ?????? ? ???-???????????????? ??????????? ??? ??????? ???????? ???????????????????.

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1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
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?????????????? ???????????? ??????? ?? ???? ???????????? (???) – ???????? ????? ?? ???????? ?????? ?????? ????????? ??????????????????, ????????????? ? ?????? ???????. ?? ?????? ??? ????? ?????????? ????????????? ??? ??????????? ??????? ?????? (???), ????????? ????? ? ?????? ??????? ?? ?????????? ?????? ???????? ??? ???????? ???????? ????? ?????? ?????????????? ?????? ? ????????? ?????????? ????????? ?? ???? ????. ??? ???????? ??????????? ???????? ?? ????????????????? ??????????????? (???????????????) [14,24] ? ??????????? [30] ??????? ???????, ????????????, ? ????????, ??? ????????? ???????? ??????????? (??) ? ??????????? ????????????? (??), ? ????? ?????????? ?????????? ????????????? ???????, ??????? ???????? ???????????? ?? ?????????? ????? [24]. ? ????????? ???? ??? ????????? ????????????? ??????? ??? ? ????????????? ???????? ???????? ???????????? ?????? ?????? – ?????? ????????? ???????, ???????? ???????? ?????????? ?? ???????????? ????????? ?????? ? ????????? ????? ?????????????? ?????????? ??????? ??? ??????? ? ??????, ??????? ???????????? ?????????? ????????? ??????????? ??????? ? ?????????.

????????? ????? ???????? ????????, ??????????? ? ?????????? ?? ??????? ???????.

????????
????????
1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
??????????.
??????????
1. ? ?????????? ???????????? ? ?????????????.

?? ??????????? ?????????????? ???????????? – ??? ??????????? ????????? ?????????????? ??????? (???) ?????????, ????????????? ?? ???? ??? ? ???????????????? ???????????? ????????? ??? ????????????? ?????? ???????? ????????? (????????????? ??????) ?? ?????????? ??????????? ??????? [64].

????????, ??? ?????? ??? ???????????? ???????? ??? ? ????????? ??????? ??????????? [16,28]. ? ???? ??????? ???????????? ? ?????????????? ??? ????? ?????????? ?????????? ???????? ?????????? ??????????????? ?????? ? ?????????? ??????? ???????????????????? ????????? ??????? ? ????????? [6,7,10,12,21].

? ??????????? ????????????????? ????????, ????? ??? ?????????? ?? (? ??????????? ?????? ? ????? ?????? ?????????) [9,10,21], ???????????? ?????? [17,28] ? ????????? ??????????????? ??????-???????, ? ????????? ???????????? ?????????????-???????????? (??) ??????? ? ??????????? ????????? ????????????????? ????????? (?????????????: IL-1, 6, ??????? ??????? ???????: TNF-? ? ??.). ??? ???????? ? ????? ??????? – ???????? ? ?????????? ????????? ?????????? ??????? ??????? – ICAM-1, ICAM-2 (intracellular adhesion molecules), VCAM-1 (vascular cell adhesion molecules), ????????? ? ??. ? ???????? ????????? ?????????????? ???????? ???????, ? ? ?????? ???????? ?????????? ? ??????????? (?) ?????, ????????????? ?? ?????? ? ? ??????????? ?????? (???). ??????? ? ? ??????????? ???????? ? ????????????? ? ????????? ? ????????? ??? ????????? [33,64], ??????? ? ??? ?????? ????????????? ??????????, ??? ???????? ?????? ?????, ????????? ????????? ??????, ????????? ? ?????? ??????????? ???? ? ????????? ????? ???? ?????? ? ?????????.

????????? ?????????????? ? ????????? ????????? ??-??????? ?? ?????????? ?????????? ???????????? ? ????????????, ??? ??????? ?? ?????? ?????????? ????????? ??????? ????????? ??????, ?? ? ????????? ??????? ??? ???????????????? ??? ? ?????????????, ? ????? ??? ???????? ?? ?????????? [6,7,12].

??? ??? ? ????????????? ????????-???????? (??? ???), ???????? ?????? ????? ?????? ? – ??????????, ???????????? ?????? (??), ?????????????, ? ????? ?????????????? ???????? ??????? [8,9], ????????? ? ??????? ??????????? ???????????, ?????????? ?????????????, ????? ? ???????????? ???????????? ???????? [9], ? ????? ? ????????? ??????????? ?????????? ?????? ??????????????????? ?????????.

1.1 ???????????????? ??????? ?????? ?????? ? ????? ? ??? ???????? ??? ? ?????????????.

? ????? ? ?????? ????????????? ? ???????????????? ??????? ????? ??, ? ??? ????? – ????? ?????? (?????), ?????? (????) ? ??????? ????????? (????). ?? ???????? ?????? ???????? – ???????????? (??), ???????????, ????? ?? ? ????????? ??. ???????? ????????? ?? ??????????? ?????????? ???????? ????????? (???). ????????? ? ?????? ??????? ? ????????? ?????????????? ? ? ??????? ????????? ???????? ?????: ?????????? ??????????? ? ? ??????? ???????? ?? ??????, ? ????????????? – ?????????. ??, ?? ? ?????? ??????, ????? ?????????? ? ????????? ???????????????? ? ?????????????? ?????? ? ? ? ??????? ?????????? (??) ? ?? ????? ?????? ????????? (?????). ????? ??? ???????????? ??????? ???????????? ??-??????? ?????????? ??????, ? ?? ??????? (???????? ?? ? ?? ????????????? ????????? - ????) ???????????????? ? ????? ??????????? ????????. ? ????? ????? ???????? ????? (????? ????) ? ? ???????????? ? ????, ???????, ??????? ???????? ???????????? ?????? ??, ?????????? ??? ?????. ?????????, ??? ?????? ???? ? ? ??????? ??????? ????? ???????? ????????? ???????????? ????????? ?? [7,10].

???? ????????? ?? ????????? ????? ????????-??????????????? ??????????. ??????????? [49], ??? 75% ?????????? ? ???? (????-?) ????????? ?? ???????? ?. ????????? ???????? ????-??????? ???????? ????? ????-100 ? ????. ? ?????????????? ???? ?? ?? [7,11,21], ??????? ?????? ? ?????? ????????? ? ???????? ? ????????? ?? ?????????. ??? ??????????? ??????????? ?????? ??? ??? ?????????? ??????????? ?? ? ?????, ? ? ??????????? ?????? ????-100 ? ???-?, ?? ????????? ? ?????????? ?????????? ????-?, ? ????? ????????????? ?????????? ???? ? ??????. ???? ???????? ???????? ?????? ?? ???????????? [11,31,49,81] ? ???????????? ?????????? ??????? ?????????. ???? ????????, ??? ????????? ????????????? ? ???????? ???? ? ?????????? ????????, ???????? ???????? ???, ???????? ? ???????? ????????? ??????? ???? ? ?????. ?????????????????? ?????? ?? ??????? ?? ???????????????? ?, ?? ??????? ?? ?? ????????????. ??????????????? ? ??????????? ??????? ???? ??????, ??? ???????? ??????? ? ???????????? ??-?????????? ?? ??????????? ?????? [26].

????? ???????, ???????? ??????? ? ? ??????????? ????????? ?????????? ??????????? ? ??????? ????????? ? ??, ?? ??????????, ? ????? ? ????????? ?? ??????????????? ???????. ? ???????? ?????????? ???, ? ????? ???????? ?????? ??????????? ???????? ??? ??????? ? ?????????? ??? ???????????, ???? ? ??????? ??????? ???????????? ????????? ??????????????? ????????? ?????? ??-???? ? ????????? ?, ?????? ?????, ? ????? ?.

??? ?????????? ??? ? ????????? ??????? ???????????? ?? ? ?????? ????? ?????????? ???????????????? ??????? ?????? ?. ?????? ????? ?????????? ????????????? ??????? ????-? ?? ????????? ?. ??? ???? ? ? ????????? ??????? ???????????????? ??, ??????? ????????? ?????????? ????, ?????????????? ?? ?????? ????-? [32,49]. ?????????, ??? ????? ?? ???????? ???????? ????????????? ???????? ??????? ????-? ? ??????????? ????????? ????????? ?? ?? ?????????. ? ????????? ??? ??????? ????-100 ???????????? ?????????? ? ????? ????????????? ????. ? 95% ??? ????????? ???????? ?????????????? (?????????) ?, ?????? ? ~ 5% ???????, ????? ??????????? ?????? [28]. ?????? ??????????? ??????? ?????????? ???????????? ??????? ??????? ????????? ??? ????-100.

???????? ???????????? ????????? ????????? ??????????? ???? ????????????? ???????????? ?? ??????????? ????? ? ?????????? ??????????? ????????????? ????-?. ??? ?????????? ???? ???????? ?? ??????????? ????? ?? ??????????? ????????? ???? ? ?? ????????? ? ??? ????? ??????????????? ???????? ?????????????. ??????? ?????????? ?? ??????????? ? ??? ???? ???????????? ? ???????? [81].

????????, ??? ????????? ? ???? ????????? ?? ??????????? ?? ?????? ?, ?? ? ?????? ??-????, ? ??? ????? ? ??, ? ??????? ??????? ???????????? ?????????????? ???? ??????????? ??????? ???? – ????? ?? ????????? [7,10]. ?????????, ??? ??????? ???? ? ?? [10] ??? ???????? ?? ???????? ? ???????? ? ??????? ?????????, ??, ? ? ??????????? ????????? ????????????????? ? ???????????????? ??????? – ?-????. ? ?????????? ?-???? ? ?????? ?????? ????????? ??????? ??????????? [21,22,27], ? ?? ??? ???? ???????????? ? ????????? ???????? ?????? ? ?????????? ?????????????? ???????????. ???????????????? ???? ???????????? ???????????? ???????????, ?????????????? ?? ??????????? ?? (“?????????”-?????????), ?????????????? ? ???????????, ?? ?? ???-???????????, ????????????? ????? ????????, ?? ?? ???????????? ? ??? ??????????? ?????????.

?????????? ??? ???? ?????????????? ???? ????????? ?? ? ?? ?? ????????? ? ???????? ????-?????., ??????????????? ??????? ????????? ??. ???? ????? ?????? ? ????????? ??????? ??????? ?????, ????? 90% ??? ????????????? ?, ? ????????? ????? ???????? ?? ???? [22,57,61]. ???? ?????????????? ???????? ?? ? ? ? “?????” ????-?. ??? ???? ???? ??????????????? ? ?????????? ????????? – ??????????? ????????? ????????, ????????????? ????? ? ? ???????????????. ??????? ????????? ?? ??????? ?????? ?? ?????? ?????????? ??????????? ???? [55]. ? ????? ? knockout ?? ????-????, ??? ?????????? ??????????? ? ????? ????? ? ?? ??? ???? ??? ??????? ????? ????????? ??????????? ??????? ????????????. ????????, ???????? ??????????????? ???? ??? ??????????????? ??? ???? ? ???????? ? ??????? ????????????? ????????? ? ???????? ??, ??????????? ?? ? ????????? ??????????????????? ????????? [48,55,60].

?? ??????? ????????? (????) – ???????? ??????????????? ?????????, ????????????? ?? ?? ?????????????? ?????? (? ?.?. ? ?? ?????? ???????) ? ?????? ??? ??? ??????????? [7,21]. ???????? ?????? ????? ??????? ???????? ????-I. ???? ????? ? ????????? ? ???? ?????????????? ? ? [10,20,21]. ???????????, ??? ? ????? ? ??????????? ????-? ? ?????????????? ?????????????? ???????? ????????????? ????-I ????????? ? ???????????? ????????? ??????????????????? ????????? ????? [66]. ??????????????? ????????????? ????-I-???? ? ??????????? ????????, ??????????? ?? ??????????? ?????, ???????? ??????? ???? ????? ? ????????? ? ????????????? ???????? ??????????????????? ????????? ????? [44]. ??? ???????? ????????????? ? ???????? ????????? ?????????? ????, ????-I ? ????????? ? ????-I ? ??????? ???? ? ?????????? ?? ??????? [13].

????? ???????, ??? ???????? ??? ? ????????????? ????????? ????????? ?????????????? ?????????????? ???????????????? ??????? ?????? ?. ????????? ?? ?????????????? ????? ????? ???????? ? ???????? ??????????? ???????? ?????????? ?????????????????? ???????, ????????????? ? ???????? ??????? ? ???????????????? ???.

1.2 ?????????? ?????????????????? ??????? ??? ?????? ???????? ??? ? ?????????????.

???????????????? ??????? ?????????????????? ??????? ? ????????? ?????????????? ? ??????? ???? ??????: ??????? ?????????????? ?????????, ?????????? ???????? ??-????, ? ??????? ?????????? ?????, ?????????? ?????????? ??????????? ??????????.

?????? ??-???? ???????????? ?????? - ?????????????? ????? ?????? ?????????. ? ????? ?? ?????????????? ??????? ?????????? ????? ????????? ????????????????? ????????, ?????????????? ? ??????? ???? ????????? ??????? ??????????: ??????????????????, ?????????????? ?????????????, ? ?????????????????, ?????????????? ??????????? ?????????? ??????? ?????? (??????????????? ???????), ?? ??????????? ? ?????????????? ????????? [2].

????????, ????????????? ?? ???? ??? ? ????????????? ???????????? ??????????????????? ??????? ? ?????????????? ???, ???????? ? ????????? ?????????? ????? ? ?????????? ????????????????? ????????? ? ??????????? ? ? ?????? ???????. ??? ??????? ??????? ??? ?????????????? ??????????? ?? ??? ???, ??????? ?? ?????? ??????????????, ????????? ? ???? ??????? ???????????????? ???????????????????? ????????.

??, ??????????? ????? ?????? ??-????, ? ??????? ????????? ??????????? ?????????? ? ?????????, ????????? ? ???? ????? ???????????? ??????????? ?? ?, ????????? ?? ?????????????? ?????????? [18,19]. ????????????? ? ????? ???????????? ????????? ?????????? ? ???????? ?????? [1], ???????? ????? ??????? ? ????????????? ??????????? ??????? ? ? ????? ?????????.

????? ?? ????? ??????? – ???????? ??????????? ? ????????????? ???: ?-?????????? ????? (???), ???????????? ??????? ?, ??????????? ? ??., ??????? ??????????? ?????? ???? ? ????????? ? ????????????? ?????????????? ? ???????????? ??????? ????????? [1]. ???, ????????, ????????, ??? ??? ?????????? ???????? ?? ??-????? ??? ?? 4-7 ??? ??????????? ? ????????? ??????????????????? ??????????? ?????? ?????????? ???????????? ??? ? ?????. ??? ???? ???????????, ??? ??????????? ??????? ? ???????????? ??? ??????? ????????? [16].

??????????????, ??? ??? ?? ?????? ?????????????, ?? ??????????? ???????? ??? ? ?????????????. ???????? [15,25], ??? ??? ????????? ????-100 ??????????? ????????? ????, ????? ? ?????? ??????????? ? ?? ? ?????????? ???????????????? ????????? ?? ?????????. ???, ????????, ??? ????? ??????? ?? 90% ????????????? ????-?? [16,28].

??????????? ??????? ? ? ?????????? ??? ? ???? ??????? ????? ? ????????? ? ??????????? ???????????? ??????? ????????????? ????????? ? ??????? ?????????? ????? ?????????. ????????????? ????????? ???+??, ??????? ?? ? ???? ? ???????? ?-????, ? ???????? ?????????? ??????? ??????? ??????????? ????????? (VCAM), ?????????? ?????? ??????, ????????????? ? ??? (??????????????? ? ???? ?-????) [15,27] ? ????????? ??????????????, ????????? ??????? -?????????????? ? ????????? ???????????? ??????? [15,17].

?????????????? ??, ??????????? ? ?????????? ??????, ???????????? ???????????, ?????????? ????????????? ? ???????? ????????????? ????????, ???????? ???????, ?????? ? ?????? ?????????, ????????? ? ???????????? ???? ?????????? ?????? ???????? ???????. ?????????? ????????? ????????? ? ???????? ?????, ?? ???? ??????????????? ????????? ?-???? ? ??, ???????? ? ???????????? ? ???????? ?????????????? ?????? ?????, ?????????? ???????? ????????? ? ???????? ??????? ?????????? ?????? [15,17,21,22]. ? ???????? ????? ??????????? ???????? ????????????? ??????, ??????? ????????? ? ??????? ??????????????????? ??????????.

??? ????????????? ?????????????? ? ????????? ???????? ??????, ????????????? ??????????? ?????????? ?????? ?????????? ?????. ??????????? ???????? ?????????? ?-????????????? ????? ? ????????? ?-????? ??????????. In vitro ?????????? ?????????? ???????? ???????????????? ?????? ?????????? ????? ?? ???????. ?? ?? ????? ??????????? ? ??? ???????? ?? ??? ????? ??????? ?????????????? ????? ? ??? [4]. ??????, ? ?-????????? ????? ????????? ? ?????????? ?????????? ????????? ??????????????? (?????????? ???????????? ??????????, ????????????? ?????????? ????????????) [15], ? ??? ????? ????????? ?? ???? ?????? ???????? ?????? ?? ??????? ????????????, ?.?. ?? ???????????? ???????? ????????? ? ?????????.

??? ?????????????? ???? ??? ????? ?????????, ??? ???????????? – ??? ??????????? ??? ????????? ?? ?????????????? ?????????? ???????????? ?? ?????? ???????. ????????? ?????????? ????????????? ??????????? ?? ???? ??? (???????????? ?????????? ??????????? ????????? ??????? ?? ? ???????) ? ???????? ?????????? ? ? ???????? ??????? ? ?????????????? ?????????????? ?????????? ???????????? ?? ? ?? ? ????? [14,15].

????????
????????
1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
??????????.
??????????
2. ?????????????? ??????????? ? ????????? ??????.

??? ? 1987 ?. Goldstein ? Brown ???????????? ??????????, ??? ???????? ???????? ??????????????????? (???) ???????? ?????? ????, ?????????????? ?? ?????? ????-100 ????-????????? ?? ???????? ?. ? ??????? ??????????? ?????????? ?????????? ??????? ?? 50%, ? ??????? ???? ????? ??????? ?????, ??? ?????????? ? ?????????? ????????? ????????????? ? ??? ? ????????? ???????? ??? ? ???? ????????. ????? ??????????????? ??????? ?????????????? ? ????? ?????, ?? ?????????? ?????????? ????????? ??????????????? [34].

??? ?????????? ??????? ??????? ???? ?????????? ??????????? ?????? ??? – ??????? ???????? ? ????????????? ????????? ????? ??????? ????-? (????-100). ?????? ????????? ????? ???????. ??? ????????? ????? ???????? ?? ? ??? ????????? ?????????? ???????????? ? ????????? ???????????????????? ??????????? ????? ? ??????????????? ??????????? ?? ????? [38,39].

?? ???????? - ??????????? ???????? ? ?????????? ???????????????????? ? ?????????????? ??????? ???? ??????????? ??????? ?????????????? ? ??? ????????? ???. ??????????????? ?????????? ???????? ?????????? ? ??????? ???????????????, ? ????????? ??? ??????????????. ? ??????? ??????? ?????????? ??????? ? ?? ????????-???????? ??????????????, ??? ?????????????? ?? ??????? ??????. ???????? ??????????? ????????? ???????????????? ? ??????????????? ?????????????? ? [67,74,76], ?? ???? ???????????????? ???????? ????? ???? ???????????? ? (CyA). ??????? ?? ????????? ? ???? ???????? ???????? ?? 50-60%. ??? ???????????????? ? ??????????????? ???????? ???????? ?????? ?????????? ?? 3 ? 6 ?????? ??????????????. ????????????? ??????? ????? ???????? ?? ?????????? (????) ???????? ?. ????????????? ???????? ?????? ?????????????? ????????? ??????? [76].

? ?????? ???????????? ?????????? ?????????? ???????? ? ?? ?????????????? ??????? ?????????????? ????????????? ? ??????? ???? ?????? ????? ?? ???? ??????????????? (?y?). ??? ? ?????? ?????????? ????? ?????????????? ??????? ?? ???????? ? ??????? ?? 50% ? ??????????? ? ????? ? 8 ??????. ??????? ???? ???????? ????? ? ?????????? ????????? ?????????? ? ??????? 18 ?????? ????? ?????????????? [74].

???????????????? ???? ???????? ? ??????????? ?????????????? ????? ?. ???????? ???????? ??????????????? ??????? ???????? ?????? ? ??? “??????????” CyA. ?? ????????? ? ???????? ???????? ?? 30-60% ? ??????? 3-8 ?????? ????? ??????????????. ???????? ???? ? ?? ????????????? ????????? ?????????? ????????? ? ? ????????? ? ? ??????????? ??????????????? ????? ????-??????????. ???????????????????? ???? ????????, ??? ?????? ?????? ??? ?? ?????? ???? ????? ?????????????? ??????????? ? ????????? ? ?????????????? ??????? ????????? ?, ? ???????? ????????????? ???????? [51].

??????????? ? ??????????????? ?????????? ? ??? ??????? ???, ???? ?????????? ??????? ???-???????????????? ??????. ???????????? ??????????? ????? ?????? ??? ??????? ???????? ?? ?????- ??? ?????????????? ???????, ???????? ??? ????????????? ????-?????????. ?????????? ?????????????? ????????????????? ? ???? ?????????? ?? ???????? ???????? [41,62,77] ? ????????? [80], ?????? ????????????? ???? ?????????? ????????? ????????????? ?????? ??????????. ???? ???????????, ??? ?????????????? ???-???????????????? ? ???????? ? ???????? ?? ? ????????? ?? 30-50% ? ??????? 4 ??????? [36]. ???????????? ??????? ??????????? ?????? in vitro ???????? 70% [62,63]. ????? ????? ??? ????????? ??????????? ???????? ??????????? ??? [80], ? ??? ?????? ?? ??? ???????????.

? ??????? [63] ? 5????? - ????????? ?? ??? ??? ??????????? ????? ??????????? ??????? ?, ????? ?????????? ?? ???? ? ?????????????? 48 ?. ? ????? ? ??????? 24 ?. ???????? ??????????????? ????????????? ???????? ? ????? ????-?. ????? ?????? ????- ??? ????????? ?????????????? ????? ???????????????? ???????, ????????????? ?? ????? ????????. ????? 3 ??? ????? ???????? ??? ??????? ?????????? ?????????????????? ??????. ?? ?????????? ??????????? ? ???????????? ?? ?????????? [63].

????? ???, ?????? ????????? ??????????? ??? ???????? ?? ??? ??? ?? ???????????. ????????????? ???????? ?????? ???????????? ? (1-5%), ??????? ???? ? ?????????? ??? ?????????????? ?????????, ?? ? ?????? ?? ????? 4 ??????? [41,62,63,77]. ????????, ??? ??? ????????? ??????? ?????????? ?????????? ?????????? ???????????? ???????????? ????? ?, ? ?????????? ??????? ??????????? ? ? ????????. ???????????????? ???????? ????????????????? ? ???? ? ??????? ??????? ???????????, ?????? ??????? ?? ??????? ????????? ?? ?????????? ????, ?.?. ??? ???? ????? ???? ??? ???????? ? ????????????? [63]. ????? ????, ??? ?????????? ??????????? ???????? ??????????? ????? ???????? ???: ??????????? ????????? ?????? ?? ??????? ????????? ???????, ??????????? ?????? ?????????? ?????????? ?????????? ????-?-????, ?????????????? ??????? ?????? ??????????????????? ?????? ? ?.?. [77,79,80].

?? ?????? ?????? ?????????????, ??????????? ?? ????? ? ??????????? ????-?????, ????????? ????????? ????????? ?????? ??????????????? ???????? ?????????? ? ? ????????? ??????????? ????-????. ???? ???????????, ??? ??????????? ????-???? ? ? ???????? ???????????? ????-????? ?? 30% ?? ??????????? ??????, ??? ???? ??????????? ??? ???????????? ?? ? ????????? ? ????????? ??????????????????? ????????? ? ???????. ???? ?????????? ? ???? ????????????? ???????? 8 ?????? ????? ?????????????? ? ? ??????? ??????????? ? ? ??? ?????? 16% [59].

????????? ????????? ??? ? ????????????? ????? ?????????????? ? ????? ??????????? ? ????????????? ????????????? ???????. ???? ?????????? ??????? ?????????? ????????? ? ??? ?????????? ???????????????? ????????????? ? ??? [14,25]. ????????? ?????????????? ????????????? ????????? ?????? ?????? ???????: ???????????, ??????????????, ?????? ??????????????, ??????????? ??????? ???? ? ?????????? ????????? ???????, ??????? ??????????????? ? ?????????????? ????????? ??????, ?? ??????????????? ? ?.?. [14,22]. ???? ???????? ?????, ??? ?? ??????????? ????????? ? ???????? ??????????????? ????-????????? [3].

????????? ???????? ????????????? ????? ? ???????? (?? ?????? 8-12 ???.) ????????, ??????????? ?? ??????????? ?????, ????????? ? ???????????? ???????? ???????? ???????????? ?, ? ????? ? ?????????? ??????? ? ?????????? ?????????? ? ? ? ??????. ??????????? ????? ?????????????????? ?????????? ?????????? ??????? ? ????????????? ???????? ?????. ????? ???? ??? ?????? ??-????? ?? ???? ??????? ?????????? ????? ??????? ??????? ??????????????????? ????????? [25]. ?????????????? ??????????????????? ????????? ????? ? ???????? ????? ????????? ? ?????????? ?????????? ???????? ???????? ????? ? ??????????? ? 3 ????, ? ??? ?? ? ????????? ??????? ?????????????? ?????????, ??? ??????????? ?????? ??????????? ?????????? ?? ? ? [23].

? ??????? ???? ????? ??? ??????????? ? ????????? ?????? ???????????????? ? ????????????????? ???????? ???? ?? ???? [5] ? ??????? ???????????? ?????? ????????? ?????????????? ?? ??????? ?????????? ??????????????. ?????????? ?????????????? ????????? ???????? ??? ???????????????. ???? ????????, ??? ????????????? ??????? ??????????? ? 21 ???, ?? ??? ????????? ??????????? ?????????. ??????????? ???????????? ???????? ????? ? ????????????? ?????????? ?????????, ???????????? ?????????? ???? ??????????? ??????????????? ??????????. ????????? ??????? ? ??????????? ? ???????????? ????????? ??????? ???????????? ???????????: ???????????? ????????? ?????????? ?? 9-16%, ???????????? ??? ? ??? ????????? ?? 28% ? 22% ??????????????, ????????? ???????????, ????????? ?????? ???????????????? ????????????? (?????????? ???????? ?????????? ?? 32-53%) [12,14]. ??????? ?????? ?? ??? ???? ???????? ?? 7.1%, ?? (????) - ?? 7% ?? ????????? ?????? [5].

????? ?????? ????????? ? ?????????????? [14] ?????? ?????????? ?????? ? ????????. ??? ???? ???????? ??????? ????? ??? ?? ????????????????? ?? ????? ????? 1.5-3 ?????? ????? ??????????????. ???? ??????????? ???????? ?? ? ?? ? ??????? ?????, ? ????? (????? 1.5 ??????) ???????? ?????? ?? ? ?? ? ??????? ???? ? ?????????? ?? ? ????. ????????? ??????? ????????????? ????????? ????? ???????????, ??? ??????? ???????????????? ??????????? - ????????? ? ???????????? ????????, ?????? ?????? ?? 1-2 ???????? ?????? ??? ????????????? ? ?????????? ?? 6-12 ???????. ????? ????????? ??????? ?????????? ???????? ??? ????????? ? ??? ????????? ???????????? ??????????? ?????????????, ? ????????? ????? ??????????? ???????? [14].

????????
????????
1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
??????????.
??????????
3. ?????????????? ?????? ???????? ?????.

? ????????? 10-15 ??? ???? ????????? ?????? ????????????? ????????????????? ?? ??????? ?????? ???????????-??????????????? ???? ? ????????? ????????? ??????. ? ????????? ???? ???????????, ??? ??? ?????? ??????????? ????-????? ? ??-??????, ????? ?? ????? ??????????? ????-????????? ? «?????????»-????????? ??? ??????? ?-???? [10,37,38,57,58,73]. ????????, ??? ?????????? ?????? ??-???? ????????? (????????????? ???????????????) ???????? ? ???? ? ???????????-?????????????? ?????????????? ????????? ?????-???????????? ?????????? ?. ??? ?????????? ? ???????????? ???????? ?? ? ???? ? ????? ?????????, ?? ? ? ? ? ?????? ???????. ????????? ???????? ?? ??????????? ? ???? ?? ?????????? ???????. ? ?????? in vitro ????? ???? ????????, ??? ?????????? ?? ????????? ??? ???????????????? ???? ???????? ? ????????? ?????????? ? ? ?????????? ??? ????????? ????-?????????? [40]. ???????????? ??????? ?????????????? ?? ?? ????????? ??-?????????? ? ? ???????????? ? ???????? ????????????? ??????. ???????????, ??? ?????????? ?? ????????????? ??????????? ?????????? ???????????? ???? ? 2 ???? ? ?? ?????? ?? ?????????? ???? [29].

?????? ????????? ??? ??????????? ??????????, ??? ???????????? ?????? ??-????, ? ????? ?????????? ???????? ??????? ??? ??? ? ????????????? ???????????? ?? ???????? ??? ? ???????? ???????? ??????????? ? ?????????. ? ???????? ?????????? ?????????????????? ??????? ??? ????????????? ??????????????? ????? ? ????????? ????????????? ??????????????? ??-????????????????????? ??????? (??-???) ???????? ???????? ? ??????? ???. ???????? ??-??? ????????? ? ???????? ?? ?? 45% ? ? ???????? ??????????????????? ????????? ? ??????? ? ??????? 2 ??????. ????? ???????? ????????? ????????????? ?????????? ? ???? ???????, ?????????? ????????????? ????????? ???????????? ????? ??????? ? ????? [43].

??? ?????? ????????????????? ? ????????????? ????????????? ? ??????? ????????????? ?????????????? ?????? ? ??????? ??????????????? ???????????, ????????? ???????????? ?????????? ???????????? ??????, ?????????? ?????????????????? ?????????, ??? ?????????? ?????????? ??????? ?????????? ???? ??????. ?????? ?????????? ???????? ?????? ???????? ???????? ????? (??), ?????????? ????????? ????????? ?????? ? ?????? ??????????? ?????????? ?????? ??-???? ? ?????? ???????? (??????????) ???????. ??????? ???? ?????????? ???????????? ????? ?????????????? ?????? ???????? ????? (???) ??? ?????????????. ??? ??????????? ??????? ??????????????? ? ????????? 5 ???. ???????????? ? ??? ??????????? ????????? ????????????? ? ????????? ???????? ????? ?????? ?? ??????? ??-?????? ? ???????? ??????.

??? ???????????? ????????????? ??? ???? ??????? ??????????? ??????? ?????? ?????????????. ???????? knockout ? ???? ??????????? ????, ????????????? ?? ?????? ???? ??? ????-?????????. ? ?????????? ? ????? ???????? ??????????? ??? ? ??????? ???????????? [38,46]. ????-?????????? ???? ????? ??????? ?????? ?????? ??????? ??? III ???? ????????, ??????? ???????????? ????? ?????????????? ??????????? ? ??????? ? ???????? ????-????. ?????????, ??? ?????????????? ????????? ??? ?????????? ?????????? ?????? ?? ????-?????????? ? ?????????? ????? ????????? ? ????????? ? ?????-??????????? (? ??????????? ???? ? ?????) 10-15% ????-????? ? ????? ?? ??????????? ??????. ????? ?????????? ???? ???? ??????????, ????? ??????? ???????????? ??, ?? ? ??????? ??????????????????? ????????? [38,45,57,58,72,75]. ??? ???? ?-??? ???? ????????? ?? ???????????????? ? ?????????, ??????, ?????? ? ?????? ????? [57], ??? ??????? ? ??????? ???????????? ??????????? ?????? ??.

??? ???????????? ???? ??????????????? ???? ? ?????????????? ??? ???? ???????????, ??? ????????? ???? ?????????? ???????? ? ??????? ??????????? ?????????? ?????? ???????????? ?? ? ????????????? ??????????? ?????? [36].

????????, ??? ?????????????? ??????????? ?? ????-?????????? ????? ??????? ?? ? ????????? ?? 87% ? ????????? ??????????????????? ??????????? ????? ? 23 ????. ????? ?????????? ????????? ???? ????? ??????????, ??? ??? ? ????????????? ???(?2, ?3-??????)-???????, ??????? ??????? ?? ???? ?? 48% ? 35% ?????????????? ? ??????????? ?? ?????? ?? ??????? ?????????????. ?? ? ?????????? ????? (????? 4 ??????) ????3-?????? ??????????? ?????? ???????????? ?? [70].

?????????????? ??????????? ?? ????-?-?????????? ????? ?? ???? ??????????? ????? ? ??????????????????? ????? ?? ?????? ?? ??????????????????? ????????? ??????? [37,46]. ? ?????????? ????? ? ??????????????????? ????-?-?????????? ?? ?? ???? ??????? ????? ??????????????????? ??????????? ????? ????? ?? 63% ?????? [56].

????? ???????, ???? ????????, ??? ???????? ?????? ??? ??? ????????????? ??????, ? ????????, ? ??????????? ???????????? ???? ? ?????, ?? ???? ????????? ??? ????????? ??-????.

???????? ??? ????????????? ?? ?????????????? ??????????? ??????????? ??. ??????????????????? ?????????? ????? ??????? ?? ?? ????-?????????? ?????. ???????????? ??????? ? ????????????? ????, ?? ? ?? ????????????? ?? ???????????. ?? ????? 2 ?????? ??-????? ??????? ??????????????????? ????????? ? ??????? ? ????? ????? ???? ? 4 ???? ?????? ?? ????????? ? ????????? [71]. ? ?????? ???????????? ????-?-?????????? ?????????? ????? ????????????????? ?????????? ?? ? ???????????????? ???? ????????????? “?????????”-????????? ?. ????? ?????????????? ????????? ???????????? ?? ?? 15-25%, ???????? ? ?????, ?? ?? ????? ???????? ??????? ?? ???????? ??????????????????? ???????????, ???????? ?? ?????????? ?????????? ????????? in vitro [54]. ??????????, ?????????? ????? ??????????? ??? ?? ????-?-?????????? ?????. ????? 3 ?????? ?????????? ?? ??????????? ????? ?? ?????????? ??????? ??????? ? ????????????? ??, ?? ? ?? ?? ????????? ? ?????????, ?? ????? ???????? ?????? ? ??????? ??????????? ????? ? ????? ????? ???? ?????? [53].

? ????? ? ????????? ?????????????? ? ????????????? ??????????????? ?????? ??? ??? ?????????????, ? ????????? ?????, ? ??? ?????? ??????????? ????????? ????? ??????.

????? ???????, ???????????? ? ??? ??? ????????????? ??????????, ??? ???????? ???????? ?????? ?? ???? ? ???????? ?????? ??????????? ? ????????? ??????????????????? ????? ?????? ??? ????. ????? ????, ??? ?????? ???????? ?????? ???????? ???? ? ???????????? ??????????????????? ????????? ?????? ??????, ? ???????? ???????? ???.

????????
????????
1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
??????????.
??????????
??????????.

????????? ??????? ???????? ????? ????????????? ???????????? ??????? ??? ? ?????????????, ???? ? ??????? ??????????? ?????????????????? ??? ????????? ? ??????????? ????????.

???????? ????????????? ???????? ??????? ????????? ? ?????? ??????? ?????????????? ???? ????????????? (???, ???-III ????). ??? ???? ???????? ?????????? ????????? ??????????? ??????????????????? ?????? ???????? ?????????????? ????-???????? ? ? ???????? ???????? ?? ????? ???? – ????????.

??? ??? ???????????? ?????????????? ???-???????????????? ???? ?, ??????? ????? ??????? ??????? ????????????? ????????? ??????. ??? ???????????????? ????????????? ? ??? ???????????? ?????????????? ????????? ?????? ?, ?????? ? ????????.

????????????? ????????? ?????? ??????????? ???????? ????????????? ????????? ??????? ?? ????????? ? ???????????????? ? ???????????? ???????? ??????? ???, ??? ? ?????????????. ??????????? ?????? ????????? ???????????????? ?, ???????????? ?? ??????????????? ???????? ?, ????????????? ?????????? ?????, ???? ? ?? ???????????? ??????, ? ????? ?????????????? ?????????????? ?????????? ???????? ?? ?? ??????????? ?. ?????? ????????? ???????? ???????? ????????? ?????? – ???????????????. ???????? ??????, ?????? ???? ??????????????????, ? ??????? ???????????? ???????? ??????? ???????????? ??????????? ?????????? ????????? ????????? ????????????????? ????????? ? «????????» ???????, ????? ????????? ??????????????? ?????? ??-???? ? ?????????? [14] ? ????????? ??? ??????????? (??????????) ???????????? ????????. ???????????? ???????? ????????? ????????? ?????? ????? ???? ?????????????? ???????? ??, ? ????????? ??????? ???????????? ??????????????????????? ?????????????? ??????.

???????????? ??????????? ?????? ?? ??? ??????????????, ????? ?????????????? ?????????? ??????. ??? ????? ??????????????? ?????? ?? ????? ?? ? ?? ? ? ????? ??????????? ??? ???? ? ??-?????? ??? ????? ?????????????? ??-???????? ?. ?????? ?? ???????? ????? ????????? ?????? ????????? ? ??????????? ? ? ??? ????? ????????? ??????? ??????????? ?? ????? ????-??????????? ???????? ????????? ?? [22]. ????? ???? ?????? ?? ????? ???????????? ??????? ?, ????????????? ????? ?????? ??-????, ? ??? ????? ????? ?? ??? ?????????????.

? ????????? ????? ???????? ?????? ? ????????? ??????????????? ?????? ?? ? ?????? ?, ??? ? ???????? ??? ? ? ???????? [68,69]. ????????, ??? ? ??????? ?????????? ???? ????????????? ???????? ?????????? ?? ???????? ???????????????????? ??? ????????? ??????????????.

????? ? ? ?????? ?? ??? ???????? ?????????????????? ??????? ? ????????? ????? ???? ?????????? ???????????? ??????????? ?? ???? ????????????? ???????. ?????? ???????????? ?????? ??????? [42].

? ????????? ??????? ????????????? ???????? ????? ?????????? ???????, ??????? ??????? ???????? ??? ??????????? ???????????????? ?????????? ?????? ? ??????? ??????????? ????????.

????????
????????
1. ? ?????????? ???????????? ? ?????????????.
2. ?????????????? ??????????? ? ????????? ??????.
3. ?????????????? ?????? ???????? ?????.
??????????.
??????????
??????????

????????? ??, ??????? ??, ????????? ?? ? ?????. ???????????? ???????? ????????, ??????????????? ? ???????? ??????. ?????? ???? ???? 1991; 111; 6: 932-947
??????? ?? ???????? ? ????????????????? ???????????????? ?????????? ?????????? ? ?? ?????????????????? ??????? ??? ???????????????? ????????? ? ???????. ???? 1999; 11: 484-490
??????? ??, ????????? ??, ??????? ?? ? ?????. ?????????????? ????-??????????? ?????? ?? ??????????? ??????????? ?????? ????????. ?????? ??? ??? 1999; 5 (????.): 27-39
??????????? ?? ??????? ????????????? ??????????? ??????? ? ???????????? ????????? ?????????????? ?????????? ?????????? ?????????????? ????? ??????? ??????????? ??????????? ???????? ?????? ? ??????????????. ???????. ???…????. ???. ????, ???????????, 1989, 22 ?.
????????? ??, ??????????? ??, ????????? ?? ? ?????. ????????????? ?????? ???????????????? ????????? ?????????? ? ????????? ????????? ?????? ??? ??????? ??????? ?????????? ??????????????. ???? 1998; ????. 1: 165
?????? ??, ??????? ??, ??? ??, ??????? ?? ??????????????????? ????????? ??????? ???????????????????????? ??????? ??? ????????????????? ????????????. ???? 2000; 130; 7: 45-51
?????????????? ??, ??????????? ?? ????????????: ?????? ? ????????????, ?????????? ? ??????? ? ???????????. ??? 2000; 8; 7:
???????? ?? ??????????????????????? ??????????????? ? ?????? ???????? ????????? ? ???????????????? ??????? ? ?? ?????????. ???????. ???…???. ???. ????. ?., 1994
???????? ??, ????????? ?? ???? ?????????????????? ? ?????? ???????????? ????????. ???? 1992; 114; 10: 437-438
?????? ??, ?????????? ?? ??????, ???????????? ? ???????????? ???, "?????" 1995, 298 ?.
????? ??, ?????? ??, ??????? ?? ? ?????. ????????? ???????? ??????????? – ?????? ??? ???????? ??????????? ????????????? ? ?????? ????????. ? ??. ???????????? ????????., ?., “?????”; 1989; 71-90
????????? ??, ????????? ??, ???????? ?? ? ?????. ?????????????? ????????? ?????? ? ??????? ?????????? ?????????????? ????? ?????????? ?????????????? ????????? ????????? ??????. ???? 1998; ????. 1: 154-155
???????? ??, ??????? ??. ?????????? ???????????? ? ???????????? ??????? ????????? ?????? ?????. ? ??. ???????????? ????????., ?., “?????”; 1989; 204-230
?????????? ?? ???????????????? ??????????? ????????? ??????? ? ???????????? ? ??????????? ??????? ??????????? ??????? ??????. ???????. ???…???. ???. ????, ???????, 1999, 35?.
???????? ?? ???????????? ? ???????? ??????????. ???? 1996; 122; 7; 4-8
???????? ??, ??????? ??, ?????????? ?? ? ?????. ?????????? ? ??????? “?????? ????” ??????. ??? ??? 1998; 6: 67-74
???????? ??, ???????? ??, ???????? ?? ?????????? ??? ????????? ???????? ????????? ?????????? ? ?????????? ??????. ???????? 2000; 10: 45-50
????? ??, ???????? ??, ?????? ?? ???? ?????????????? ?????????????? ??????? ? ????????? ?????????? ????? ? ???????????? ?????? ?????? ? ??????????? ????? ????. ???? 1991; 1: 108-109
???? ??, ???????????? ??, ??????? ?? ? ?????. ??????????? ? ????????????????????? ?????????? ?????????? ?????? ? ?????? ??? ??????????? ??????. ???? 1996; 11: 494-498
????? ?? ??????????? ???????????-????????? ?????? ?????????????? ?????? ?????????????. ?., “??????”, 1987, 69 ?
????? ??, ??????? ?? ??????????????? ????? ?????? ?????????????. ?., "?????????????" 1989, 71 ?.
????? ??, ????? ?? ??????????? ????????? ????????. ?, 1998
???????? ??, ??????? ??, ???????? ?? ? ?????. ?????????????? ?????????????? ???????? ???????? ????? ????? ????? BALB/c ????? ??????????? ????????? ?????? ????????. ???? 2000; 3: 340-343
???????? ??, ??????? ??, ??????? ?? ???????? ????????-??????? ? ????????. ???? 1999; 6: 604-611
????????????? ??, ????????? ??, ????????? ?? ? ?????. ??????? ?????????????? ????????? ????? ?????? ?? ??????????????? ????????? ??? ????????????????? ?????????????. ???? 1998; ????. 1: 134-137
????? ??, ???????????? ?? I????????i ?????????? ?? ???i? ??? ???????? ??????????ii ??????????? ?????i? ?i???????i?i? ? ????????i ????i ??????. ??????????????i? (???.) 2000; 1; 1: 281-283
?????? ?? ????????????-???????????????? ???????????? ?????? ?????????, ????????????? ? ????? ????????. ?????? ? ??? ??? 1999; 5(????.): 218-239
????? ?? ???????? ????????????? ? ??????????: ????????????? ????????????? ??? ??????????????? ????????. ??? ??????? ? 1999; 5: 48-56
?????? ??, ????? ??, ????????? ?? ? ?????. ??????? ?????????? ??????? ?????????????? ????????? ?? ?????????? ????????????? ??????? ? ?????? ????????? ????????????, ????????????? ? ??????????????? ???????? ?????? ????. ???? 1993; 10: 384-386
??????? ?? ???????? ??????????? ?????????? ??????? ????????????? ?????? ????????? ?? ????????? ??????? ???????? ??????? ?????????????? ???????????????????. ???????. ???…????. ???. ???? 2000, 27?.
Abraham R, Kumar NS, Kumar GS et al. Synthesis and secretion of apo B containing lipoproteins by primary cultures of hepatocytes isolated from rats fed atherogenic diet. Atherosclerosis 1993;100; 1: 75-83
Beisiegel U. Lipoprotein metabolism. Eur Heart J 1998; 19 (suppl A): A20-A23
Bhakdi S et al Complement activation and atherogenesis. Binding of CRP to degraded, nonoxidised LDL enchances complement activation. Arterioscler Thromb Vasc Biol 1999; 19: 2348-2354
Bilheimer DW, Goldstein JL, Grundy SM, Starzl TE Liver transplantation to provide low density lipoprotem receptors and lower plasma cholesterol in a child with homo-zygous familial hypercholesterolemia. N Engl J Med 1984; 311: 1658-1664
Boisvert WA, Black AS, Curtiss LK ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE-deficient mice transplanted with ApoE-expressing macrophages. Arterioscler Thromb Vasc Biol 1999;19; 3: 525-530
Boisvert WA, Curtiss LK Elimination of macrophage-specific apolipoprotein E reduces diet-induced atherosclerosis in C57BL/6J male mice. J Lipid Res 1999; 40; 5: 806-813
Boisvert WA, Spangenberg J, Curtiss LK Role of leukocyte-specific LDL receptors on plasma lipoprotein cholesterol and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 1997; 17; 2: 340-347
Boisvert WA, Spangenberg J, Curtiss LK Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation. J Clin Invest 1995; 96; 2: 1118-1124
Buja LM, Kita T, Goldstein JL et al. Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia. Arteriosclerosis 1983; 3; 1: 87-101
Cai HJ, He ZG, Ding YN Effects of monocyte macrophages stimulation on hepatic lipoprotein receptors. Biochim Biophys Acta 1988; 958; 3 : 334-342
Chowdhury RJ, Grossman M, Gupta S, et al. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits. Science 1991; 254: 1802-1805
Cioffi L, Sturtz FG, Wittmer S et al. A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E. Gene Ther 1999; 6; 6: 1153-1159
Clinton SK, Schaub RG, Bree MP et al. Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol and carrageenan granuloma foam cell formation in Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb 1994; 14: 70-76
Duverger N, Kruth H, Emmanuel F et al. Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits. Circulation 1996; 94; 4: 713-717
Fazio S, Babaev VR, Murray AB et al. Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages. Proc Natl Acad Sci USA 1997; 94: 4647-4652
Fazio S, Hasty AH, Carter KJ et al. Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo: bone marrow transplantation studies in the mouse. J Lipid Res 1997; 38: 391-400
Fazio S, Linton F, Hasty AH, Swift L Recycling of apolipoprotein E in mouse liver. J Biol Chem 1997; 274; 12: 8247-8253
Fazio S, Sanan DA, Lee YL et al. Susceptibility to diet-induced atherosclerosis in transgenic mice expressing a dysfunctional human apolipoprotein E(Arg 112,Cys142) Arterioscler Thromb 1994; 14: 1873-1879
Goldstein JL, Brown MS Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis. Circulation 1987; 76; 3: 504- 507
Grossman M, Raper SE, Kozarsky K, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genet 1994; 6: 335-341
Gunsalus JR, Brady DA, Coulters M et al. Reduction of serum cholesterol in watanabe rabbits by xenogeneic hepatocellular transplantation. Nat Med 1997; 3; 1: 48-53
Herijgers N, Eck MV, Groot PH et al. Effect of bone marrow transplantation on lipoprotein metabolism and atherosclerosis in LDL receptor–knockout mice. Arterioscler Thromb and Vasc Biol 1997; 17:1995-2003.
Herijgers N, Eck MV, Groot PH et al. Low density lipoprotein receptor of macrophages facilitates atherosclerotic lesion formation in C57Bl/6 mice. Arterioscler Thromb Vasc Biol 2000; 20; 8: 1961-1967
Herijgers N, Winther MP, Van Eck M Effect of human scavenger receptor class a overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice. J Lipid Res 2000; 41: 1402-1409
Linton F, Hasty AH, Babaev RV, Fazio S Hepatic apoE expression is required for remnant lipoprotein clearance in the absence of the low density lipoprotein receptor. J Clin Invest 1998; 101; 8: 1726-1736
Linton MF, Babaev RV, Gleaves LA et al. A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation. J Biol Chem 1999; 274; 27: 19204-19210
Linton MF, Atkinson JB, Fazio S Prevention of atherosclerosis in apolipoprotein E- deficient mice by bone marrow transplantation. Science 1995; 276; 5200: 1034-1037
Linton MF, Fazio S Macrophages, lipoprotein metabolism, and atherosclerosis: insights from murine bone marrow transplantation studies. Curr Opin Lipidol 1999; 10; 2: 97-105
Mitchell C, Mignon A, Guidotti JE et al. Therapeutic liver repopulation in a mouse model of hypercholesterolemia. Hum Mol Genet 2000; 9; 11: 1597-1602
Mortimer BC, Redgrave TG, Spangler EA et al. Effect of human apoE4 on the clearance of chylomicron-like lipid emulsions and atherogenesis in transgenic mice. Arterioscler and Thromb 1994; 14: 1542-1552
Oram J, Yokoyama S Apolipoprotein-mediated removal of cellular cholesterol and phosphlipids. JLipid Res 1996; 37: 2473-2421
Raper SE Hepatocyte transplantation and gene therapy. Clin Transplant 1995; 9: 249 254
Raper SE, Grossman M, Rader DJ et al. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia. Ann Surg 1996; 223; 2: 116-126
Ross R Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340: 115-121
Schaub RG, Bree MP, Hayes LL et al. Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol and carrageenan granuloma foam cell formation in Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb 1994; 14: 70-76
Tangirala RK, Tsukamoto K, Chun SH et al. Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circ 1999; 100: 1816-1822
Tejera ML et al. Reduction of cholesterol levels following liver cell grafting in hyperlipidemic (WHHL) rabbits. Transplant Proc 1992; 24: 160-161
Theise ND, Badve S, Saxena R et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatol 2000; 31: 235-240
Theise ND, Nimmakayaki M, Gardner R et al. Liver from bone marrow humans. Hepatol 2000; 32: 11-16
Van Eck M, Herijgers N, Van Dijk KW et al. Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158-->Cys) on cholesterol levels and atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2000; 20; 1: 119-127
Van Eck M, Herijgers N, Vidgeon-Hart M et al. Accelerated atherosclerosis in C57Bl/6 mice transplanted with ApoE-deficient bone marrow. Atherosclerosis 2000; 150; 1: 71-80
Van Eck M, Herijgers N, Yates J et al. Bone marrow transplantation in apolipoproteinE–deficient mice. Arterioscler Thromb and Vasc Biol 1997; 17: 3117-3126
Van Eck M, Zimmermann R, Groot PH et al. Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2000; 20; 9: E53-62
Wang J, Pollak R, Bartholomew A. Sustained reductionof serum cholesterol levels following allotransplantation of parenchymal hepatocytes in Watanabe rabbits. Transplant Proc 1991; 23;1: 894-895
Weibin Shi, Xuping Wang, NJ Wang et al. Effect of Macrophage-Derived Apolipoprotein E on Established Atherosclerosis in Apolipoprotein E–Deficient Mice. Arterioscler Thromb and Vasc Biol 2000;20: 2261
Wiederkehr JC, Kondos GT, Pollak R Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit. Transplantation 1990; 50; 3: 466-71
Wilson JM, Chowdhury RN, Grossman M, et al. Temporary amelioration of hyperlipidemia in low density lipo-protein receptor-deficient rabbits transplanted with genetically modified hepatocytes. Proc Natl Acad Sci USA 1990; 87: 8437-8441
Wilson JM, Chowdhury RN, Grossman M, et al. Transplantation of allogeneic hepatocytes into LDL-receptor deficient rabbits leads to trainsien improvement in hypercholesterolemia. Clin Biotechnol 1991; 3: 21-26
Wilson JM, Grossman M Therapeutic strategies for familial hypercholesterolemia based on somatic gene transfer. Am J Cardiol 1993; 72: 59D-63D
Wilson JM, Grossman M, Raper SE, et al Clinical protocol ex vivo gene therapy of familial hypercholesterolemia. Hum Gene Ther 1992; 3; 179-222
Yokode M, Hammer RE, Ishibashi S et al. Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors. Science 1990; 250: 1273-1275

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