2018/02/15 by Andrew Durham, Andrew L Durham, Mei Y. Speer +6 · 1,082 citations
Immunology and Microbiology · Medicine · #Arterial stiffness #Biomarkers in Disease Mechanisms #Blood pressure #Calcification #Cardiology #Cardiovascular Health and Disease Prevention #Internal medicine #Medicine #Parathyroid Disorders and Treatments #Smooth muscle #Vascular smooth muscle
paper · pdf · doi:10.1093/cvr/cvy010
published in Cardiovascular Research 114(4), 590-600 (Oxford University Press)
openalex publication_date 2018/02/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Vascular calcification is associated with a significant increase in all-cause mortality and atherosclerotic plaque rupture. Calcification has been determined to be an active process driven in part by vascular smooth muscle cell (VSMC) transdifferentiation within the vascular wall. Historically, VSMC phenotype switching has been viewed as binary, with the cells able to adopt a physiological contractile phenotype or an alternate 'synthetic' phenotype in response to injury. More recent work, including lineage tracing has however revealed that VSMCs are able to adopt a number of phenotypes, including calcific (osteogenic, chondrocytic, and osteoclastic), adipogenic, and macrophagic phenotypes. Whilst the mechanisms that drive VSMC differentiation are still being elucidated it is becoming clear that medial calcification may differ in several ways from the intimal calcification seen in atherosclerotic lesions, including risk factors and specific drivers for VSMC phenotype changes and calcification. This article aims to compare and contrast the role of VSMCs in driving calcification in both atherosclerosis and in the vessel media focusing on the major drivers of calcification, including aging, uraemia, mechanical stress, oxidative stress, and inflammation. The review also discusses novel findings that have also brought attention to specific pro- and anti-calcifying proteins, extracellular vesicles, mitochondrial dysfunction, and a uraemic milieu as major determinants of vascular calcification.