title: Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage.
abstract: 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.
authors.affiliation: CVPath, International Registry of Pathology, Gaithersburg, MD 20878, USA. rvirmani@cvpath.org
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Allen P
authors.initials: AP
authors.lastname: Burke
authors.forename: Aloke V
authors.initials: AV
authors.lastname: Finn
authors.forename: Herman K
authors.initials: HK
authors.lastname: Gold
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Tulenko
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wrenn
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
mesh_terms: D000818:Animals; D003324:Coronary Artery Disease / Q000150:complications / Q000473:pathology*; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology*; D006801:Humans; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology*; D012421:Rupture