This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perrault, L. P. Articles by Vanhoutte, P. M. Search for Related Content PubMed PubMed Citation Articles by Perrault, L. P. Articles by Vanhoutte, P. M. Related Collections Animal models of human disease CV surgery: transplantation, ventricular assistance, cardiomyopathy Coronary circulation Lipid and lipoprotein metabolism Endothelium/vascular type/nitric oxide

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:728.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Hypercholesterolemia Increases Coronary Endothelial Dysfunction, Lipid Content, and Accelerated Atherosclerosis After Heart Transplantation

Louis P. Perrault; Florence Mahlberg; Christine Breugnot; Jean-Pierre Bidouard; Nicole Villeneuve; Jean-Paul Vilaine; Paul M. Vanhoutte

From the Research Center and Department of Surgery (L.P.P.), Montreal Heart Institute, Montreal, Quebec, Canada, and Institut de Recherches Servier (F.M., C.B., J.-P.B., N.V., J.-P.V., P.M.V.), Suresnes, France.

Correspondence to Paul M. Vanhoutte, MD, PhD, Institut de Recherches Internationales Servier, 6 place des Pléiades, 92415 Courbevoie, France.

Abstract—Hyperlipidemia may increase endothelial damage and promote accelerated atherogenesis in graft coronary vasculopathy. To study the effects of hypercholesterolemia on coronary endothelial dysfunction, intimal hyperplasia, and lipid content, a porcine model of heterotopic heart transplantation, allowing nonacute rejection without immunosuppressive drugs, was used. A high cholesterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native and transplanted hearts from cholesterol-fed animals was studied in organ chambers 30 days after implantation and compared with endothelial function in arteries from animals fed a normal diet. The total serum cholesterol increased 3-fold in donors and recipients. Endothelium-dependent relaxations to serotonin, to the ₂-adrenergic agonist UK14,304, and to the direct G-protein activator sodium fluoride were decreased significantly in allografted hearts compared with native hearts from both groups. Relaxations to the calcium ionophore A23187 and bradykinin were decreased significantly in allografts from animals fed the high cholesterol diet. The prevalence of intimal hyperplasia was significantly increased in coronary arteries from hypercholesterolemic swine. There was a significant increase in the lipid content of allograft arteries of hypercholesterolemic recipients. Hypercholesterolemia causes a general coronary endothelial dysfunction, increases the prevalence of intimal hyperplasia, and augments the incorporation of lipids in the vascular wall after heart transplantation. Hyperlipidemia accelerates graft coronary atherosclerosis through its effects on the endothelium.

Key Words: endothelium • lipids • coronary arteries • transplantation • atherosclerosis

This article has been cited by other articles:

				S. L Koshman, L. D Lalonde, I. Burton, W. J Tymchak, and G. J Pearson Supratherapeutic Response to Ezetimibe Administered with Cyclosporine Ann. Pharmacother., September 1, 2005; 39(9): 1561 - 1565. [Abstract] [Full Text] [PDF]

				C. Giannattasio, M. Failla, S. Lucchina, C. Zazzeron, V. Scotti, A. Capra, L. Viscardi, F. Bianchi, G. Vitale, M. Lanzetta, et al. Arterial Stiffening Influence of Sympathetic Nerve Activity: Evidence From Hand Transplantation in Humans Hypertension, April 1, 2005; 45(4): 608 - 611. [Abstract] [Full Text] [PDF]