Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities
Miguel Á. Ortega, Diego De León-Oliva, M.J. Gimeno, Diego Liviu Boaru, Oscar Fraile‐Μartinez, Cielo García‐Montero, Amador Velazquez de Castro, Silvestra Barrena-Blázquez, Laura López-González, Silvia Amor, Natalio García‐Honduvilla, Julia Buján, Luis G. Guijarro, Elisa Castillo-Ruiz, Miguel Ángel Álvarez-Mon, Agustı́n Albillos, Melchor Álvarez‐Mon, Raúl Dı́az, Miguel A. Sáez
Abstract
). 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.