Circulation. 2004;110:2032-2038
Published online before print September 27, 2004, doi: 10.1161/01.CIR.0000143233.87854.23
Published online before print September 27, 2004, doi: 10.1161/01.CIR.0000143233.87854.23
(Circulation. 2004;110:2032-2038.)
© 2004 American Heart Association, Inc.
Vascular Medicine |
Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta
Implications for Plaque Vulnerability
From the Cardiovascular Institute (P.R.M., K.R.P., V.F., S.K.S., J.J.B.), Mount Sinai School of Medicine, New York, NY, and the Linda and Jack Gill Heart Institute (P.R.M., D.E., H.T., W.N.O.), University of Kentucky, Lexington.
Correspondence to Pedro R. Moreno, MD, Cardiovascular Institute, One Gustave L. Levy Place, Box 1030, New York, NY 10029. E-mail pedro.moreno{at}msnyuhealth.org
Received June 26, 2002; de novo received March 18, 2004; revision received June 22, 2004; accepted June 22, 2004.
Background— Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupture. Accordingly, we tested this hypothesis by investigating whether microvessels in the tunica media, the base of the plaque, and the fibrous cap are increased in ruptured atherosclerotic plaques in human aorta.
Methods and Results— Microvessels, defined as CD34-positive tubuloluminal capillaries recognized in cross-sectional and longitudinal profiles, were quantified in 269 advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes and smooth muscle cells were defined as CD68/CD3-positive and 
-actin–positive cells. Total microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, microvessel density was increased in lesions with severe macrophage infiltration at the fibrous cap (P=0.0001) and at the shoulders of the plaque (P=0.0001). In addition, microvessel density was also increased in lesions with intraplaque hemorrhage (P=0.04) and in thin-cap fibroatheromas (P=0.038). Logistic regression analysis identified plaque base microvessel density (P=0.003) as an independent correlate to plaque rupture.
Conclusions— Thus, neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Furthermore, microvessel density is increased in lesions with inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture.
Key Words: atherosclerosis • plaque • inflammation • aorta
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