UP-REGULATION OF CELL-ADHESION MOLECULES AND THE PRESENCE OF LOW-GRADE INFLAMMATION IN HUMAN CHRONIC HEART-FAILURE

Background In the present study, the hypothesis was tested that cell a dhesion molecules are expressed in failing human hearts and that a chr onic inflammatory process contributes to chronic degeneration known to occur in cardiac incompetence. The cell adhesion molecules: ICAM-1, V CAM-1, PECAM-1, and E-selectin were studied, in addition to cellular m arkers of inflammation. Methods and results Tissue was obtained at tra nsplantation from patients with either myocarditis, chronic ischaemic heart disease, or dilated cardiomyopathy. Controls were taken from pat ients with normal ventricles. Cell adhesion molecules were qualitative ly evaluated and counted using specific antibodies and confocal micros copy. Additionally, semiquantitative evaluation of the presence of the CD3 antigen (T-lymphocytes), CD68 (macrophages), CD11a/CD18 (ICAM-1 r eceptor) and human tumour necrosis factor-alpha were used as indicator s of chronic inflammation. PECAM-1 stained all endothelial cells but I CAM-1 was only present in 80% of all capillaries in control tissue. Th e ratio ICAM-1/PECAM-1 was significantly enhanced in all groups of dis eased hearts. Myocytes in myocarditic hearts expressed ICAM-ICAM. CD3 positive lymphocytes, CD68 positive macrophages and CD11a/CD18 positiv e cells were more abundantly present than in control. Macrophages expr essing tumour necrosis factor-alpha were found in failing myocardium b ut not in control tissue. Conclusion Independent of the cause of heart failure, chronic low grade inflammation is present in failing human m yocardium. This may significantly contribute to the structural deterio ration that is the basis of reduced cardiac function in congestive hea rt failure.