Macrophage Heterogeneity Complicates Reversal of Calcification in Cardiovascular Tissues

Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic Plaque Formation Reveals Osteoclast-specific Protein Expression

“…The v1b2 subunit of the same complex, which is also highly expressed in osteoclasts, was likewise increased in atherosclerotic mouse aortas. Notably, we observed Tcirg1 expression in macrophages, thus adding to recent evidence for a role of those cells in mineral clearance within atherosclerotic plaques ( 81 , 82 ) and suggesting that macrophages adapt an osteoclast-like gene expression program and providing a possible functional mechanism. Osteoclastic V-ATPase is directly involved in bone resorption as it dissolves minerals through continuous expulsion of H + and Cl − ions ( 83 ).…”

Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice

“…For instance, the polarization of osteal macrophages might affect bone biology and metabolism in opposite ways, consistent with the role of macrophage subpopulations in the pathophysiology of various inflammatory diseases [12]. Consistently, macrophage heterogeneity was shown to modulate also vascular calcification by favoring either mineral deposition (M2 macrophages) or resorption (M1 macrophages) [45]. Noteworthy, as mentioned above, galectin-3 sustains alternative (M2) macrophage activation [17,18]; accordingly, the bone expression levels of the M2 macrophage marker Tgfb and the anti-inflammatory cytokine Il10 were reduced in Lgals3 -/mice.…”

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

“…A better understanding of the molecular mechanisms by which macrophages differentiate into osteoclast-like or into osteoblast-like cells will be needed to advance research in this area. In the future, the key issue will be to determine whether and how macrophages can be targeted to prevent excessive CVC in subject with CKD [96]. In particular, it will be important to establish whether macrophages’ anti-calcific activities can be induced without causing the cells to lose their beneficial roles in inflammation resolution or in promoting osteogenic pathways in vascular/valvular cells.…”

“…Recent data have suggested that macrophage polarization also contributes to low osteoclastic activity in human calcified atherosclerotic plaques [96]. In a recent study, Chinetti-Gbaguidi et al showed that macrophages surrounding the Ca/P deposits in human atherosclerotic plaques express CA2 and a relatively low level of cathepsin K [97].…”

“…Among the molecular mechanisms involved, the authors showed that IL-4-induced polarization lowers the expression level of the cathepsin K transcriptional regulator nuclear factor of activated T cells type c-1 (NFATC1) as well as its induction by RANKL/MCSF, through upregulation of NFATC1 promoter level of the repressive histone 3 lysine 27 trimethylation (H3K27me3). According to the authors, IL-4 induced the inhibition of the ERK-c-fos-NFATc-1 pathway and may also be responsible for the impaired mineral resorption of these osteoclast-like cells [96]. In the same manner, Nagy and colleagues studied the impact of M1 polarization on the resorbing capacity of cardiac valve monocytes.…”