Tissue Endothelin-1 Immunoreactivity in the Active Coronary Atherosclerotic Plaque

Abstract

Background The pathomorphological substrate of complicated coronary atherosclerotic lesions underlying unstable angina is characterized by a localized chronic inflammatory process. Functionally, coronary lesions associated with unstable angina demonstrate an enhanced vasoreactivity. Endothelin-1 is a potent vasoconstrictor peptide produced not only by endothelial cells but also by macrophages and polymorphonuclear leukocytes, the cell types characteristic of inflammation. Methods and Results By use of immunohistochemical techniques, we examined the presence of endothelin-1 in coronary atherosclerotic plaque tissue obtained by directional coronary atherectomy of primary lesions from 50 consecutive patients. The tissue specimens of 43 of 50 patients (86%) demonstrated endothelin-1–like immunoreactivity. Endothelin-1–like immunoreactivity preferentially localized to macrophage-rich areas, to hypercellular regions rich in microvessels, and to plaque areas with evidence of prior hemorrhage. Double-immunolabeling revealed that both macrophages (HAM56 positive) and intimal smooth muscle cells (α-actin positive) demonstrated cytoplasmic immunostaining for endothelin-1. Semiquantitative analysis of endothelin-1–like immunostaining revealed significantly ( P <.005) higher staining grades in active (1.86±0.15, n=40) compared with nonactive lesions (0.78±0.35, n=10): endothelin-1 staining grades were significantly ( P <.001) lower in patients with stable angina (0.69±0.19, n=13) than in patients with crescendo angina (1.82±0.30, n=11), with angina at rest (2.08±0.21, n=12), or with angina after myocardial infarction (2.0±0.26, n=14). Conclusions 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.