Angiogenesis in the atherosclerotic plaque

Abstract

Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis

“…Neocapillaries inside the atherosclerotic plaque are more fragile and can easily undergo damage due to the high level of oxidative stress that mainly occurs during the later stage of atherosclerosis. This latter condition could lead to plaque rupture, one of the main factors responsible for cardiovascular events [4]. Arterial injuries are followed by arterio-intimal angiogenesis that induces intimal hyperplasia and a subsequent intimal hemorrhage [38].…”

“…In fact, VEGF can stimulate endothelial cell survival, invasion and migration into surrounding tissues and increase proliferation and vascular permeability. On the other hand, during atherosclerosis, VEGF may enhance the pathophysiologic mechanism of plaque formation and destabilization by increasing the risk of plaque rupture [4,5].…”

Vascular endothelial growth factor gene transfer therapy for coronary artery disease: A systematic review and meta‐analysis

“…Moreover, adenovirus vectors may increase the risk of inflammatory activation, while most of these adverse effects alleviated after discontinuing treatment. However, more attention still should be paid to the use of VEGF gene transfer for angiogenic diseases, such as atherosclerotic disease, rheumatoid disease, retinal disease, and malignant tumors …”

Proteases: Pivot Points in Functional Proteomics

“…Chymase activates pro-MMP-9 whereas tryptase activates pro-MMP-1, −2 and −3, all involved in the development of atherosclerosis and abdominal aortic aneurysm. Extracellular matrix degradation by elevated MMPs facilitates chemokine- and angiogenic factor-triggered migration of leukocytes and endothelial cells, which accompanies neovascularization and growth of the atherosclerotic lesion, and eventually facilitates plaque rupture [119]. Chymase-activated TGF-β1 disrupts endothelial function and also contributes to intima thickening.…”