Chronic Congestive Heart Failure Is Associated With a Phenotypic Shift of Intramyocardial Endothelial Cells

Abstract

Background There is evidence that patients with chronic congestive heart failure have endothelial cell–related abnormalities of the peripheral 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 studied cardiac explants (n=19) and autopsy hearts (n=5) of patients with chronic congestive heart failure caused by either a dilated cardiomyopathy (n=12) or ischemic heart disease (n=12) and compared them with normal hearts (n=12). The antigenic expression obtained with several endothelial cell markers (factor VIII–related antigen, EN-4, Ulex europaeus agglutinin–1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], or E-selectin) was compared by use of immunohistochemical 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 percentage 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 cardiomyopathies showed a marked increase in the number of PAL-E–positive endothelial cells. Vessels with a muscular media were PAL-E–negative. Two-sample analysis revealed a statistically significant difference between hearts 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 ICAM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative. Conclusions A phenotypic shift in endothelial antigen expression of the coronary microvasculature occurs in both ischemic hearts and hearts with dilated cardiomyopathies, as revealed by PAL-E, compared with control hearts. The change may relate to compensatory mechanisms in long-standing chronic heart failure.