Thrombospondins: A Role in Cardiovascular Disease

International Journal of Molecular Sciences

Dimitry A. Chistiakov¹  Andrey V. Grechko²  Veronika A. Myasoedova³  Alexandra A. Melnichenko³  Alexander N. Orekhov³ 

[1] Department of Fundamental and Applied Neurobiology, Serbsky Federal Medical Research Center of Psychiatry and Narcology, 119991 Moscow, Russia;Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 109240 Moscow, Russia;Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 125315 Moscow, Russia;

关键词: thrombospondins;    cardiac remodeling;    cardiac hypertrophy;    heart failure;    atherosclerosis;    myocardial infarction;    cardiac fibrosis;   

DOI  :  10.3390/ijms18071540

来源: DOAJ

【 摘 要 】

Thrombospondins (TSPs) represent extracellular matrix (ECM) proteins belonging to the TSP family that comprises five members. All TSPs have a complex multidomain structure that permits the interaction with various partners including other ECM proteins, cytokines, receptors, growth factors, etc. Among TSPs, TSP1, TSP2, and TSP4 are the most studied and functionally tested. TSP1 possesses anti-angiogenic activity and is able to activate transforming growth factor (TGF)-β, a potent profibrotic and anti-inflammatory factor. Both TSP2 and TSP4 are implicated in the control of ECM composition in hypertrophic hearts. TSP1, TSP2, and TSP4 also influence cardiac remodeling by affecting collagen production, activity of matrix metalloproteinases and TGF-β signaling, myofibroblast differentiation, cardiomyocyte apoptosis, and stretch-mediated enhancement of myocardial contraction. The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of TSPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis. Targeting of TSPs has a significant therapeutic value for treatment of cardiovascular disease. The activation of cardiac TSP signaling in stress and pressure overload may be therefore beneficial.

【 授权许可】

Unknown