EFFECT OF THE ANTIOXIDANT PROBUCOL ON TRANSPLANT ARTERIOSCLEROSIS IN AORTA ALLOGRAFTED RABBITS

被引：10

作者：

ANDERSEN, HO

HOLM, P

NORDESTGAARD, BG

HANSEN, BF

KJELDSEN, K

ELINDER, LS

STENDER, S

机构：

[1] RIGSHOSP, DEPT CLIN BIOCHEM, DK-2100 COPENHAGEN 0, DENMARK

[2] HERLEV HOSP, DEPT CLIN CHEM, COPENHAGEN, DENMARK

[3] HVIDOVRE UNIV HOSP, DEPT PATHOL, COPENHAGEN, DENMARK

[4] KAROLINSKA INST, KING GUSTAF V RES INST, HUDDINGE, SWEDEN

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 1995年 / 27卷 / 08期

关键词：

AORTA-ALLOGRAFTED RABBIT; ANTIOXIDATION; CHOLESTEROL-CLAMPING; PROBUCOL; TRANSPLANTATION; ARTERIOSCLEROSIS; MACROPHAGES;

D O I：

10.1016/S0022-2828(95)90392-5

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The attenuation of atherogenesis by oral probucol treatment, demonstrated in several animal studies, has been attributed to the antioxidative property of probucol. It is thought that probucol, by inhibiting oxidation of low density lipoproteins (LDL), decreases the uptake of LDL into monocytes, and thereby reduces the development of foam cells and fatty streaks. Also, the neointimal proliferation seen after balloon injury has been attenuated by treatment with probucol, Since foam cells and neointimal proliferation are both important elements of transplant arteriosclerosis, we have investigated whether probucol might also retard the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as a bypass graft onto the abdominal aorta of another rabbit. Nine rabbits were treated with Ig probucol per day and seven animals were treated with vehicle. After a recovery period of 2 weeks, all rabbits were clamped at a human level of plasma cholesterol (6 to 7 mmol/l) for a period of 3 weeks. The amount of dietary cholesterol necessary for this clamping tended to be higher in probucol treated than in vehicle-treated rabbits. The distribution of plasma cholesterol between lipoprotein classes was similar in the two groups, except for the concentration of high density lipoproteins (HDL), which was significantly lowered by probucol. Probucol markedly decreased the susceptibility of LDL and intermediate density lipoprotein plus very low density lipoprotein (IDL+VLDL) particles to oxidation, as measured by the production of conjugated dienes when adding CU2+, Despite this, the development of transplant arteriosclerosis as well as the number of macrophages in the neointima were not significantly different in the aortic allografts from the two groups. These results suggest that antioxidative agents do not retard the development of experimental transplant arteriosclerosis. (C) 1995 Academic Press Limited.

引用

页码：1561 / 1571

页数：11

共 43 条

[1] Alonso D.R., Starek P.K., Minick R., Studies on the pathogenesis of atheroarteriosclerosis induced in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia, Am J Pathol, 87, pp. 415-435, (1977)
[2] Andersen H.O., Madsen G., Nordestgaard B.G., Hansen B.F., Kjeldsen K., Stender S., Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability, Arterioscler Thromb, 14, pp. 944-950, (1994)
[3] Baumann D.S., Doblas M., Schonfeld G., Sicard G.A., Daugherty A., Probucol reduces the cellularity of aortic intimal thickening at anastomotic regions adjacent to prosthetic grafts in cholesterol-fed rabbits, Arterioscler Thromb, 14, pp. 162-167, (1994)
[4] Billingham M.E., Cardiac transplant atherosclerosis, Transplant Proc, 19, pp. 19-25, (1987)
[5] Bjorkheim I., Henriksson-Freyschuss A., Diczfalusy O.U., Berglund L., Henriksson P., The antioxidant butylated hydroxytoluene protects against atherosclerosis, Arterioscler Thromb, 11, pp. 15-22, (1991)
[6] Carew T.E., Schwenke D.C., Steinberg D., Antiatherogenic effect of probucol unrelated to its hypo-cholesterolemic effect: Evidence that antioxidants in vim can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbi, Proc Natl Acad Sci USA, 84, pp. 7725-7729, (1987)
[7] Chancerelle Y., Lorgeril M., Viret R., Dureaurenaud G., Kergonou S.J.F., Increased lipid peroxidation in cyclosporin-treated heart transplant recipients, Am J Cardiol, 68, pp. 813-816, (1991)
[8] Daugherty A., Oida K., Sobel B.E., Schonfeld G., Dependence of metabolic and structural heterogeneity of cholesterol ester-rich very low density lipoproteins on the duration of cholesterol feeding in rabbits, J Clin Invest, 82, pp. 562-570, (1988)
[9] Daugherty A., Zweifel B.S., Schonfeld G., Probucol attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits, Br J Pharmacol, 98, pp. 612-618, (1989)
[10] Daugherty A., Zwiefel B.S., Schonfeld G., The effects of probucol on the progression of atherosclerosis in mature Watanabe Heritable Hyperlipidaemic rabbits, Br J Pharm, 103, pp. 1013-1018, (1991)

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