Role of Macrophages in the Progression and Regression of Vascular Calcification

Abstract

Vascular calcification is an abnormal cell-mediated process in which bone-specific hydroxyapatite crystals are actively deposited on the blood vessel wall and is a significant pathological basis for the increased incidence and mortality of adverse cardiovascular events. Macrophages play an important regulatory role in the occurrence, development, and regression of vascular calcification. After the tissue microenvironment changes, macrophages subsequently change their polarity and phenotype or secrete functional substances as an adaptive response. As research on macrophages continue to move into this field, we gain a new understanding of the mechanism of the formation and regression of vascular calcification, which might offer valuable new intervention targets for the prevention and inhibition of vascular calcification. This review summarizes a wealth of research in this field and explores the roles of macrophages in the development process of vascular calcification.

The Paradox Effect of Calcification in Carotid Atherosclerosis: Microcalcification Is Correlated with Plaque Instability

“…The evidence that the presence of micro-and macrocalcifications is related to a different macrophages' polarization could provide a scientific rationale capable to explain both the genesis of these calcium deposits and their different association with the carotid plaque stability. As already established for coronary plaques [31], our results suggest that carotid plaque calcifications develop by the inflammation-dependent mechanisms involved in progression and regression of atherosclerosis. The presence of high number of M1 macrophages in carotid instable plaques with microcalcifications could trigger the calcium deposition in the context of the atheroma's necrotic core by inducing vesicle-mediated mineralization process related to both macrophages and vascular smooth muscle cells (VSMCs) apoptosis [32].…”

Regular Dietary Intake of Palmitate Causes Vascular and Valvular Calcification in a Rabbit Model

“…The observed drop in monocyte count could be due to higher recruitment of blood monocytes in vascular or valvular tissues and their subsequent differentiation into macrophages, a key event in the initiation of the calcification process ( 40 ). The fact that monocyte counts were negatively correlated with both aortic valve calcification and PA/PUFA ratios in DAG might reveal novel mechanistic clues, which warrants further investigations.…”

Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall

“…Other functional substances secreted by macrophages include osteogenic genes such as tissue nonspecific alkaline phosphatase (TNAP), osteoprotegerin (OPN), and runt-related transcription factor 2 (Runx2), which further promote the osteogenic process [ 61 ]. Additionally, a recent study by Dube et al showcased that the M1 subtype of macrophages differentiated from mice bone marrow-derived macrophage (BMDM) exhibits osteogenic properties via the constitutive activation of BMP-2 signaling [ 62 ].…”

“…This complex then allows the entrance of calcium ions into the vesicles. The calcium and phosphate ions that enter the MVs via phosphate channels form calcium phosphorus complexes, which accumulate, forming the initial hydroxyapatite crystals [ 61 ]. These hydroxyapatite crystals continue to grow, rupturing the membrane, and keep growing to form calcified nodules.…”