PROMINENCE OF CORONARY ARTERIAL-WALL LIPIDS IN HUMAN HEART ALLOGRAFTS- IMPLICATIONS FOR PATHOGENESIS OF ALLOGRAFT ARTERIOPATHY

Transplant arteriopathy is a major late complication ill human heart a llograft recipients and the pathogenesis of such arteriopathy remains uncertain, The degree to which lipids and atheromata are involved irt the arteriopathic lesions remains unsettled and there is uncertainty r egarding the significance of insudation or retention of lipids within the coronary artery walls of transplanted hearts, On current immunosup pressive regimens, most patients experience an increased serum total c holesterol and low-density lipoprotein cholesterol after transplant El evation of these blood lipids has an undetermined relationship to arte riopathy, We carried out morphological, morphometric, immunohistochemi cal, ultrastructural, and biochemical studies of particular coronary a rtery segments from 23 unselected explant or autopsy allografts and do nor 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 accum ulation of lipids in both intimal and medial walls was documented by o il red O positivity, immunohistochemical staining (muscle-specific alp ha-actin), transmission and scanning electron microscopy, and biochemi cal analysis, Mean total cholesterol, esterified cholesterol, free cho lesterol, and phospholipid content (mu g/cm(2) intimal surface area) a nd concentration (mu g/mg dry defatted weight) in arteriopathic corona ries were >10-fold higher than in comparable native coronary segments. Extent of lipids in the arterial walls was highly correlated with dig itized percent luminal narrowing, mean daily and cumulative cyclospori n dose, and mean cumulative prednisone dose, Our data suggests strongl y that lipid accumulation is an important early and persistent phenome non in the development of transplant arteriopathy.