Lp. Perrault et al., Hypercholesterolemia increases coronary endothelial dysfunction, lipid content, and accelerated atherosclerosis after heart transplantation, ART THROM V, 20(3), 2000, pp. 728-736
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.