CHRONIC CONGESTIVE-HEART-FAILURE IS ASSOCIATED WITH A PHENOTYPIC SHIFT OF INTRAMYOCARDIAL ENDOTHELIAL-CELLS

Background There is evidence that patients with chronic congestive hea rt failure have endothelial cell-related abnormalities of the peripher al circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive heart failure. Methods and Results We stud ied cardiac explants (n=19) and autopsy hearts (n=5) of patients with chronic congestive heart failure caused by either a dilated cardiomyop athy (n=12) or ischemic heart disease (n=12) and compared them with no rmal hearts (n=12). The antigenic expression obtained with several end othelial cell markers (factor VIII-related antigen, EN-4, Ulex europae us agglutinin-1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhe sion molecule [VCAM], or E-selectin) was compared by use of immunohist ochemical techniques. On the basis of the initial findings, the number of PAL-E- and EN-4-positive vessels was counted. The incidence of PAL -E-positive vessels per area was quantified and related to the percent age of heart muscle cells and the total number of vessels per area. In control hearts, endothelial cells rarely were positive for PAL-E. In hearts of patients with ischemic cardiomyopathies, there was distinct staining with this marker. Hearts of patients with dilated cardiomyopa thies showed a marked increase in the number of PAL-E-positive endothe lial cells. Vessels with a muscular media were PAL-E-negative. Two-sam ple analysis revealed a statistically significant difference between h earts with dilated cardiomyopathies and ischemic cardiomyopathies (P<. 01), between hearts with dilated cardiomyopathies and control hearts ( P<.01), and between hearts with ischemic cardiomyopathies and control hearts (P<.01). Endoglin and ICBM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative. Conclusions A phenoty pic shift in endothelial antigen expression of the coronary microvascu lature occurs in both ischemic hearts and hearts with dilated cardiomy opathies, as revealed by PAL-E, compared with control hearts. The chan ge may relate to compensatory mechanisms in long-standing chronic hear t failure.