Controlling the angiogenic switch in developing atherosclerotic plaques: Possible targets for therapeutic intervention
Open Access
- 1 January 2009
- journal article
- Published by Publiverse Online S.R.L in Journal of Angiogenesis Research
- Vol. 1 (1), 4
- https://doi.org/10.1186/2040-2384-1-4
Abstract
Plaque angiogenesis may have an important role in the development of atherosclerosis. Vasa vasorum angiogenesis and medial infiltration provides nutrients to the developing and expanding intima and therefore, may prevent cellular death and contribute to plaque growth and stabilization in early lesions. However in more advanced plaques, inflammatory cell infiltration, and concomitant production of numerous pro-angiogenic cytokines may be responsible for induction of uncontrolled neointimal microvessel proliferation resulting in production of immature and fragile neovessels similar to that seen in tumour development. These could contribute to development of an unstable haemorrhagic rupture-prone environment. Increasing evidence has suggested that the expression of intimal neovessels is directly related to the stage of plaque development, the risk of plaque rupture, and subsequently, the presence of symptomatic disease, the timing of ischemic neurological events and myocardial/cerebral infarction. Despite this, there is conflicting evidence regarding the causal relationship between neovessel expression and plaque thrombosis with some in vivo experimental models suggesting the contrary and as yet, few direct mediators of angiogenesis have been identified and associated with plaque instability in vivo. 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.Keywords
This publication has 69 references indexed in Scilit:
- Extracellular Matrix Molecules: Potential Targets in PharmacotherapyPharmacological Reviews, 2009
- Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemiaBasic Research in Cardiology, 2009
- The Antiangiogenic Activity of rPAI-1 23 Inhibits Vasa Vasorum and Growth of Atherosclerotic PlaqueCirculation Research, 2009
- Ang-1 Gene Therapy Inhibits Hypoxia-Inducible Factor-1α (HIF-1α)-Prolyl-4-Hydroxylase-2, Stabilizes HIF-1α Expression, and Normalizes Immature Vasculature in db/db MiceDiabetes, 2008
- Imaging of the vasa vasorumNature Clinical Practice Cardiovascular Medicine, 2008
- Effects of Nebivolol on Endothelial Gene Expression during Oxidative Stress in Human Umbilical Vein Endothelial CellsMediators of Inflammation, 2008
- Transcriptome-wide analysis of blood vessels laser captured from human skin and chronic wound-edge tissueProceedings of the National Academy of Sciences of the United States of America, 2007
- Signaling and Functions of Angiopoietin-1 in Vascular ProtectionCirculation Research, 2006
- A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Tumor Angiogenesis: Therapeutic ImplicationsThe New England Journal of Medicine, 1971