[Differential reaction of human cardiac macro- and microvascular endothelial cells with respect to leucocyte adhesion and exposition to atherogenic lipoproteins].
While the cellular mechanisms of atherosclerosis have been intensively studied, the mechanisms leading to preferential localization of atherosclerotic lesions are less well understood. To further define these mechanisms, endothelial cells from coronary arteries, i.e., vessels with frequent atherosclerotic lesions, were isolated and grown in vitro. In order to compare the reactions of both cell types, endothelial cells derived from microvessels of human hearts were isolated and cultured under identical conditions. Incubation of endothelial cells with oxidized LDL (75 microg/ml protein) induced a significant increase in PAI-1 activity (182%, p < 0.05) in coronary macrovascular endothelial cells. This stimulatory effect of ox-LDL was less significant in microvascular endothelial cells (144%, p < 0.05). n-LDL did not influence secreted PAI-1 activity. Stimulation with angiotensin II induced expression of E-selectin more effectively in coronary macrovascular than in microvascular endothelial cells. In addition, angiotensin II-induced E-selectin expression led to increased E-selectin-dependent adhesion of HL60 cells to coronary macrovascular endothelial cells under flow conditions, while only little effect was observed with cardiac microvascular endothelial cells. In contrast, L-selectin-dependent adhesion, which has been shown to play an important role in inflammatory reactions, was preferentially observed in cardiac microvascular endothelial cells and could only be stimulated with TNFalpha, not by angiotensin II. Therefore, these cellular differences may in part explain specific properties of cardiac endothelial cells: Such that atherosclerotic lesions are localized in macrovascular vessel segments, whereas inflammatory responses are predominantly found in the microvasculature.
Gräfe
M
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Abteilung Innere Medizin/Kardiologie, Deutsches Herzzentrum Berlin und Charité-Campus, Virchow-Klinikum, Humboldt-Universität Berlin, Augustenburger Platz 1, D-13353 Berlin.
Zakrzewicz
A
A
Graf
K
K
Gaehtgens
P
P
Fleck
E
E
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D019041:L-Selectin / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D008833:Microcirculation / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D017395:Plasminogen Activator Inhibitor 1; D019041:L-Selectin