Abstract
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) trans-differentiation 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, 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 focussing on the major drivers of calcification, including aging, uremia, 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 uremic milieu as major determinants of vascular calcification.
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, 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 focussing on the major drivers of calcification, including aging, uremia, 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 uremic milieu as major determinants of vascular calcification.
| Original language | English |
|---|---|
| Pages (from-to) | 590–600 |
| Journal | Cardiovascular Research |
| Volume | 114 |
| Issue number | 4 |
| Early online date | 5 Mar 2018 |
| DOIs | |
| Publication status | Published - 15 Mar 2018 |