Title:Cartilage Oligomeric Matrix Protein: Matricellular and Matricrine Signaling in Cardiovascular Homeostasis and Disease
Volume: 15
Issue: 3
Author(s): Yi Fu and Wei Kong*
Affiliation:
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191,China
Keywords:
COMP, ADAMTS-7, interactome, atherosclerosis, calcification, restenosis, thrombosis, dilated cardiomyopathy.
Abstract: Cardiovascular (CV) diseases remain a leading cause of morbidity and mortality in the world.
Increasing the understanding of the pathogenesis of various CV diseases may provide novel therapeutic
targets to improve their prevention and treatment. Cartilage oligomeric matrix protein (COMP), also
known as thrombospondin-5 (TSP-5), is a matricellular protein that is abundantly expressed in both cartilage
and the CV system. Our group and others have identified COMP as playing critical roles in maintaining
CV homeostasis. COMP, expressed and produced by vascular smooth muscle cells (VSMCs), maintains
VSMC contractile phenotypes. COMP deficiency enhances VSMC migration and aggravates VSMC
calcification and atherosclerosis. Moreover, a lack of COMP leads to spontaneous dilated cardiomyopathy
in mice. COMP is also secreted by platelets in circulating blood and negatively regulates haemostasis and
thrombosis. A series of COMP binding proteins, such as integrin α7β1, integrin β3, thrombin, and bone
morphogenetic protein 2, have been identified in the CV system, and they have been determined to mediate
various COMP functions. The matrix metalloproteinase (A Disintegrin and Metalloproteinase with
Thrombospondin motifs) ADAMTS-7 is a regulatory enzyme that is responsible for the degradation of
COMP in the CV system. ADAMTS-7 expression correlates with atherosclerosis and vascular calcification
in both human genome-wide association studies and in vivo mice models via COMP-dependent and
COMP-independent mechanisms. In this review, we summarize what is currently known about the matricellular
and matricrine signaling of COMP mediated by its respective binding partners as well as its
proteolytic regulation by ADAMTS-7 in CV disease.
