Prominence of coronary arterial wall lipids in human heart allografts. Implications for pathogenesis of allograft arteriopathy.

Abstract

Transplant arteriopathy is a major late complication in human heart allograft recipients and the pathogenesis of such arteriopathy remains uncertain. The degree to which lipids and atheromata are involved in the arteriopathic lesions remains unsettled, and there is uncertainty regarding the significance of insudation or retention of lipids within the coronary artery walls of transplanted hearts. On current immunosuppressive regimens, most patients experience an increased serum total cholesterol and low-density lipoprotein cholesterol after transplant. Elevation of these blood lipids has an undetermined relationship to arteriopathy. We carried out morphological, morphometric, immunohistochemical, ultrastructural, and biochemical studies of particular coronary artery segments from 23 unselected explant or autopsy allografts and donor age-matched native coronary controls. Patients died of cardiac and non-cardiac reasons over a period of 4 to 1610 days after transplant. Atheromata were frequent, and diffuse intra- and extra-cellular accumulation of lipids in both intimal and medial walls was documented by oil red O positivity, immunohistochemical staining (muscle-specific alpha-actin), transmission and scanning electron microscopy, and biochemical analysis. Mean total cholesterol, esterified cholesterol, free cholesterol, and phospholipid content (microgram/cm2 intimal surface area) and concentration (microgram/mg dry defatted weight) in arteriopathic coronaries were > 10-fold higher than in comparable native coronary segments. Extent of lipids in the arterial walls was highly correlated with digitized percent luminal narrowing, mean daily and cumulative cyclosporin dose, and mean cumulative prednisone dose. Our data suggests strongly that lipid accumulation is an important early and persistent phenomenon in the development of transplant arteriopathy.