Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification

Abstract

Rationale: Intimal calcification is highly correlated with atherosclerotic plaque burden, but the underlying mechanism is poorly understood. We recently reported that cartilage oligomeric matrix protein (COMP), a component of vascular extracellular matrix, is an endogenous inhibitor of vascular smooth muscle cell calcification. Objective:

COMP-lex Mechanics

“…Fu and colleagues highlight the important contributions and additive effects of mesenchymal and hematopoetic lineage cells in calcific vasculopathy. 1 Their findings are in agreement with previous lineage tracing studies showing that both VSMC and marrow-derived cells contribute to biomineralization in atherosclerotic lesions. 21 Direct effects of activated monocyte/macrophages on vascular cell calcification were first described in 2000 through the potent pro-osteochondrogenic cytokine, TNF-a.…”

“…Similar to the findings by Fu and colleagues in this issue of Circulation Research , 1 Di Cesare and colleagues showed that COMP interacts with cells via the integrin receptor, alpha 5 beta 1. 6 Interestingly, given that Du et al showed that COMP binds to BMP-2, 14 an alternative mechanical phenomenon may take place (Figure 2).…”

“…Fu and colleagues 1 also provide strong support for earlier findings, highlighting the role of inflammation in atherosclerotic calcification. The authors demonstrate that bone marrow-derived inflammatory cells are increased in the circulation of COMP-deficient hyperlipidemic mice.…”

“…The findings by Fu and colleagues 1 support the importance of matricrine signaling, a less appreciated mechanism of intercellular communication, but an important additional layer of control for cellular behavior and differentiation.…”

“…In this issue of Circulation Research , Fu and colleagues 1 highlight the important role of the non-collagenous ECM protein, cartilage oligomeric matrix protein (COMP) in calcific atherosclerosis. COMP, a member of the thrombospondin family of proteins (TSP-5), maintains cartilage structural integrity by binding collagen and other ECM proteins, such as aggrecan (chondroitin sulfate proteoglycan 1), aggregates of which give cartilage its springy resistance to compression.…”