Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2054-2061
Published online before print July 21, 2005, doi: 10.1161/01.ATV.0000178991.71605.18
Published online before print July 21, 2005, doi: 10.1161/01.ATV.0000178991.71605.18
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© 2005 American Heart Association, Inc.
Brief Reviews |
Atherosclerotic Plaque Progression and Vulnerability to Rupture
Angiogenesis as a Source of Intraplaque Hemorrhage
From the CVPath, International Registry of Pathology (R.V., F.D.K.), Gaithersburg, Md; Department of Pathology (A.P.B.), University of Maryland, Baltimore; Cardiac Unit (H.K.G., A.V.F.), Department of Internal Medicine, Massachusetts General Hospital, Boston; Department of Surgery (T.N.T.), Thomas Jefferson University, Philadelphia, Pa; Department of Chemical Engineering (S.P.W.), Drexel University, Philadelphia, Pa; and Department of Cardiology (J.N.), University of California, Irvine.
Correspondence to Renu Virmani, MD, Medical Director, CVPath, International Registry of Pathology, 19 Firstfield Rd, Gaithersburg, MD 20878. E-mail rvirmani{at}cvpath.org
Observational studies of necrotic core progression identify intraplaque hemorrhage as a critical factor in atherosclerotic plaque growth and destabilization. The rapid accumulation of erythrocyte membranes causes an abrupt change in plaque substrate characterized by increased free cholesterol within the lipid core and excessive macrophage infiltration. Neoangiogenesis is associated closely with plaque progression, and microvascular incompetence is a likely source of intraplaque hemorrhage. Intimal neovascularization is predominantly thought to arise from the adventitia, where there are a plethora of pre-existing vasa vasorum. In lesions that have early necrotic cores, the majority of vessels invading from the adventitia occur at specific sites of medial wall disruption. A breech in the medial wall likely facilitates the rapid in-growth of microvessels from the adventitia, and exposure to an atherosclerotic environment stimulates abnormal vascular development characterized by disorganized branching and immature endothelial tubes with "leaky" imperfect linings. This network of immature blood vessels is a viable source of intraplaque hemorrhage providing erythrocyte-derived phospholipids and free cholesterol. The rapid change in plaque substrate caused by the excessive accumulation of erythrocytes may promote the transition from a stable to an unstable lesion. This review discusses the potential role of intraplaque vasa vasorum in lesion instability as it relates to plaque rupture.
Intraplaque hemorrhage is a major contributor to coronary lesion progression. The formation of immature blood vessels within a plaque promotes red blood cell leakage, an important source of free cholesterol. This review discusses the potential role of angiogenesis in lesion instability as it relates to plaque rupture.
Key Words: angiogenesis • plaque rupture • sudden coronary death • free cholesterol • hemorrhage
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