Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities

Abstract

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO₄^3- and ionized calcium (Ca²⁺). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Keywords: biomarkers; endothelial cells (ECs); signaling pathways; vascular calcification; vascular smooth muscle cells (VSMCs).

Figure 1

Schematic representation of the main anatomical locations susceptible to the deposition of calcium salts: blood vessels, aortic valves, breast cancer, brain, tendons, or kidneys. In black appear the anatomical locations of calcium deposits and in red the related diseases. FIBGC: familial idiopathic basal ganglia calcification, AD: Alzheimer’s disease, CAVD: calcific aortic valve disease, MI: myocardial infarction, CKD: chronic kidney disease, PAD: peripheral artery disease.