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Front. Cardiovasc. Med. | doi: 10.3389/fcvm.2018.00027

Cell Phenotype Transitions in Vascular Calcification

 Luis Hortells1, Swastika Sur1 and  Cynthia St. Hilaire1, 2*
  • 1Department of Medicine, University of Pittsburgh, United States
  • 2Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, United States

Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC); vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

Keywords: Vascular Calcification, vascular smooth muscle cell, endothelial cell, Valve interstitial cell, calcification, Valve calcification, arterial calcification, phenotypic plasticity, Endothelial to mesenchymal transition

Received: 01 Jan 2018; Accepted: 14 Mar 2018.

Edited by:

Joshua D. Hutcheson, Florida International University, United States

Reviewed by:

Jose J. Fuster, School of Medicine, Boston University, United States
Vicky E. MacRae, University of Edinburgh, United Kingdom  

Copyright: © 2018 Hortells, Sur and St. Hilaire. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Cynthia St. Hilaire, University of Pittsburgh, Department of Medicine, 200 Lothrop Street, 1744 Biomedical Science Tower, Pittsburgh, 15260, PA, United States,