Hypercholesterolemia increases coronary endothelial dysfunction, lipid content, and accelerated atherosclerosis after heart transplantation

Hyperlipidemia may increase endothelial damage and promote accelerated athe rogenesis in graft coronary vasculopathy. To study the effects of hyperchol esterolemia on coronary endothelial dysfunction, intimal hyperplasia, and l ipid content, a porcine model of heterotopic heart transplantation, allowin g nonacute rejection without immunosuppressive drugs, was used. A high chol esterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native an d transplanted hearts From cholesterol-fed animals was studied in organ cha mbers 30 days after implantation and compared with endothelial function in arteries from animals' fed a normal diet. The total serum cholesterol incre ased 3-fold in donors and recipients. Endothelium-dependent relaxations to serotonin, to the alpha(2)-adrenergic agonist UK14,304, and to the direct G -protein activator sodium fluoride were decreased significantly in allograf ted hearts compared with native hearts from both groups. Relaxations,to the calcium ionophore A23187 and bradykinin were decreased significantly in al lografts from animals fed the high cholesterol diet. The prevalence of inti mal hyperplasia was significantly increased in coronary arteries from. hype rcholesterolemic swine. There was a significant increase in the lipid conte nt of allograft: arteries of hypercholesterolemic recipients. Hypercholeste rolemia causes a general coronary endothelial dysfunction, increases the pr evalence of intimal hyperplasia, and augments the incorporation of lipids i n the vascular wall after heart: transplantation Hyperlipidemia-accelerates graft coronary atherosclerosis through its effects on the endothelium.