Tissue Endothelin-1 Immunoreactivity in the Active Coronary Atherosclerotic Plaque

Abstract

Endothelin-1 immunostaining of atherosclerotic tissue localizes predominantly with plaque components indicative of chronic inflammatory processes. The increased tissue endothelin-1-like immunoreactivity in active coronary atherosclerotic lesions may provide a clue to the mechanisms of increased vasoreactivity of the culprit lesion in acute ischemic syndromes, which is the clinical substrate of the active coronary atherosclerotic plaque.

Endothelial Function

“…Moreover, the release of the potent vasoconstrictor endothelin-1, which is characteristic of endothelial dysfunction, is enhanced at the site of the unstable plaque, further mediating focal vasoconstriction and myocardial ischemia. 24,25 The enhanced vasoconstriction at the site of the active plaque may escalate further in response to such stimuli as physical and mental stress, which mediate vasoconstriction via an endothelium-dependent mechanism.…”

Endothelin Receptor Blockers in Cardiovascular Disease

“…56 Tissue ET levels have been shown to correlate with the severity of angina in patients with coronary artery disease and increase in patients with unstable angina. 57,58 ET-1 plasma levels have also been found to be elevated in patients with acute myocardial infarction and correlate with 1-year prognosis. 59 No clinical trials have yet been conducted to evaluate the effect of ET receptor blockade on the development of chronic atherosclerotic vascular disease.…”

Endothelin-1 and Vascular Tone in Subjects With Atherogenic Risk Factors

“…Although ET-1 was initially discovered as a product of endothelial cells, 34 it is also secreted by macrophages and activated vascular smooth muscle cells. 10,[35][36][37] Recent evidence evaluating the expression of coronary ET-1 at different stages of atherosclerosis reveals that ET-1 expression increases with progression of atherosclerotic lesions, and ET-1 immunoreactivity is particularly elevated in the presence of inflammation. 36,37 Indeed, we have previously shown that endogenous ET-1 contributes to vasomotor tone in atherosclerotic coronary arteries.…”