The role of thrombospondin-1 in cardiovascular health and pathology

Krishna, Smriti Murali, and Golledge, Jonathan (2013) The role of thrombospondin-1 in cardiovascular health and pathology. International Journal of Cardiology, 168 (2). pp. 692-706.

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Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality in the developed world and are becoming increasingly prevalent in the developing world. Although a range of therapies already exist for established CVDs, there is a significant interest in further understanding disease pathogenesis in order to improve treatment. Thrombospondin (TSP)-1 is an important extracellular matrix component that influences the function of vascular smooth muscle cells, endothelial cells, fibroblasts and inflammatory cells with important implications for CVDs. TSP-1 regulates matrix production and organisation thereby influencing tissue remodelling and promoting the generation of T regulatory cells that control the inflammatory response. Reported findings from in vitro and animal studies are conflicting and suggest differing effects of TSP-1 on various cellular mechanisms, depending on the experimental setting. Vascular cells express a number of TSP-1 receptors, such as CD36, proteoglycans and several integrins, which are regulated by specific contextual signals which may explain the varying effects that TSP-1 elicits in different environments. Different domains of TSP-1 activate distinct signalling pathways eventually resulting in quite different cellular phenotypes and tissue specific effects. The sum total of the various pathways activated likely determines the overall effect on angiogenesis or proliferation in a specific tissue. Hence defining a common mechanism of action of TSP-1 in CVD is complicated. Increasing the understanding of the role of TSP-1 in various CVDs will potentially provide new opportunities for therapeutic intervention using peptides derived from its various domains currently under evaluation in other diseases.

Item ID: 30172
Item Type: Article (Research - C1)
ISSN: 1874-1754
Keywords: thrombospondin-1, cardiovascular diseases, transforming growth factor-beta 1, thrombosis, matrix remodelling
Funders: National Health and Medical Research Council (NHMRC), BUPA, Queensland Government
Projects and Grants: NHMRC project grant 540404, NHMRC project grant 1003707, NHMRC project grant 1021416, NHMRC project grant 1020955, NHMRC Centre of Research Excellence fellowship 1019921
Date Deposited: 13 Nov 2013 05:40
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 75%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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