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Vascular Cell  2009 

Controlling the angiogenic switch in developing atherosclerotic plaques: Possible targets for therapeutic intervention

DOI: 10.1186/2040-2384-1-4

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In recent years, an increasing number of angiogenic therapeutic targets have been proposed in order to facilitate modulation of neovascularization and its consequences in diseases such as cancer and macular degeneration. A complete knowledge of the mechanisms responsible for initiation of adventitial vessel proliferation, their extension into the intimal regions and possible de-novo synthesis of neovessels following differentiation of bone-marrow-derived stem cells is required in order to contemplate potential single or combinational anti-angiogenic therapies. In this review, we will examine the importance of angiogenesis in complicated plaque development, describe the current knowledge of molecular mechanisms of its initiation and maintenance, and discuss possible future anti-angiogenic therapies to control plaque stability.According to a World Health Organization Fact Sheet (EURO/03/06) cardiovascular disease (CVD) is the number one killer in Europe, with heart disease and stroke being the major cause of death in all 53 Member States. Figures show that 34,421 (23% of all non-communicable diseases) of Europeans died from CVD in 2005. The report also highlighted the fact that there is approximately a 10-fold difference in premature CVD mortality between Western Europe and countries in Central and Eastern Europe with a higher occurrence of CVD amongst the poor and vulnerable. Although improvements in understanding have helped to reduce the number of Western European dying from CVD and related diseases further advances will require a clearer understanding of the pathobiological mechanisms responsible for the development of stroke, atherosclerosis and myocardial infarction. Approximately 75% of acute coronary events and 60% of symptomatic carotid artery disease are associated with disruption of atherosclerotic plaques [1]. In 1971, Folkman [2]introduced the concept of angiogenesis as a necessity for tumour growth. Its importance in other pathological conditions, includ


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