The Elusive Origin of Atherosclerotic Plaque Calcification

Abstract

It has been known for decades or even centuries that arteries calcify as they age. Vascular calcification probably affects all adults, since virtually all have atherosclerotic plaques: an accumulation of lipids, inflammatory cells, necrotic debris, and calcium phosphate crystals. A high vascular calcium score is associated with a high cardiovascular mortality risk, and relatively recent data suggest that even microcalcifications that form in early plaques may destabilize plaques and trigger a cardiovascular event. If the cellular and molecular mechanisms of plaque calcification have been relatively well characterized in mice, human plaques appear to calcify through different mechanisms that remain obscure. In this context, we will first review articles reporting the location and features of early calcifications in human plaques and then review the articles that explored the mechanisms though which human and mouse plaques calcify.

The Interplay Between Brain Vascular Calcification and Microglia

“…Upregulated BMP signaling induces proinflammatory effects in endothelial cells ( Cai et al, 2012 ). Aortic calcification is known to be associated with inflammation and dependent on BMP2 signaling ( Canet-Soulas et al, 2021 ). It remains to be investigated whether deregulated expression of Bmp2 and Bmp4 contributes to vascular inflammation and calcification in Pdgfb ret/ret mice ( Torok et al, 2021 ).…”

Roles of Macrophages in Atherogenesis

“…Besides Mφs, vascular smooth muscle cells (VSMCs) can also transdifferentiate into lesional Mφ-like cells through cholesterol loading (Rong et al, 2003). Advanced plaques are characterized by subendothelial deposition of lipids, necrotic cell debris, calcium phosphate crystals, fibrosis, and inflammatory immune cells including Mφs, T and B lymphocytes, neutrophils, dendritic cells (Canet-Soulas et al, 2021). Lesional T cells can recognize local antigens, leading to activation, clonal expansion, and cytokine production (Robertson and Hansson, 2006).…”

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair

“…As cells die, calcifications may occur. The exact mechanisms of plaque calcifications are still unclear [ 34 ].…”