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Chronic congestive heart failure is associated with a phenotypic shift of intramyocardial endothelial cells
M M Marijianowski1, M van Laar, J Bras
1Department of Cardiovascular Pathology, University of Amsterdam, The Netherlands.
Insights
Chronic heart failure alters coronary microvasculature endothelial cells, showing increased PAL-E expression in dilated and ischemic cardiomyopathies compared to controls. This phenotypic shift may reflect compensatory mechanisms in heart failure.
Area of Science:
- Cardiovascular Research
- Endothelial Cell Biology
- Heart Failure Pathophysiology
Background:
- Patients with chronic congestive heart failure exhibit endothelial cell abnormalities in peripheral and coronary circulation.
- Previous studies suggest a link between endothelial dysfunction and heart failure, necessitating further investigation into coronary microvasculature.
- Understanding these changes is crucial for developing targeted therapies for heart failure patients.
Purpose of the Study:
- To investigate the phenotypic expression of endothelial cells in the coronary microvasculature of patients with chronic congestive heart failure.
- To compare endothelial cell marker expression in hearts with dilated cardiomyopathy and ischemic heart disease against normal controls.
- To identify specific endothelial cell markers associated with heart failure pathophysiology.
Main Methods:
- Cardiac explants and autopsy hearts from patients with dilated cardiomyopathy (n=12), ischemic heart disease (n=12), and normal controls (n=12) were analyzed.
- Immunohistochemical techniques were employed to assess the antigenic expression of endothelial cell markers (e.g., PAL-E, endoglin) and adhesion molecules (e.g., ICAM, VCAM).
- Quantitative analysis focused on the incidence of PAL-E-positive vessels per area and its relation to heart muscle cells and total vessels.
Main Results:
- A significant increase in PAL-E-positive endothelial cells was observed in hearts with dilated cardiomyopathies and ischemic heart disease compared to control hearts (P < .01).
- PAL-E staining was distinct in ischemic cardiomyopathies and markedly increased in dilated cardiomyopathies, indicating a phenotypic shift.
- Endoglin and ICAM showed positive staining but were not discriminating; endothelin, VCAM, and E-selectin were negative.
Conclusions:
- A phenotypic shift in endothelial antigen expression, specifically involving PAL-E, occurs in the coronary microvasculature of hearts affected by both ischemic and dilated cardiomyopathies.
- This observed change in endothelial cells may represent a compensatory response to long-standing chronic heart failure.
- Further research into these endothelial alterations could reveal novel therapeutic targets for managing heart failure.
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.