Format

Send to

Choose Destination
Biochim Biophys Acta. 2015 Apr;1849(4):448-53. doi: 10.1016/j.bbagrm.2014.06.004. Epub 2014 Jun 15.

Epigenetic regulation of smooth muscle cell plasticity.

Author information

1
Agnes Ginges Laboratory for Diseases of the Aorta, Centre for the Endothelium, Vascular Biology Program, Centenary Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Australia.
2
Departments of Internal Medicine and Pharmacology, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University, New Haven, CT 06511, USA.
3
Departments of Internal Medicine and Pharmacology, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University, New Haven, CT 06511, USA. Electronic address: kathleen.martin@yale.edu.

Abstract

Smooth muscle cells (SMC) are the major cell type in blood vessels. Their principal function in the body is to regulate blood flow and pressure through vessel wall contraction and relaxation. Unlike many other mature cell types in the adult body, SMC do not terminally differentiate but retain a remarkable plasticity. They have the unique ability to toggle between a differentiated and quiescent "contractile" state and a highly proliferative and migratory "synthetic" phenotype in response to environmental stresses. While there have been major advances in our understanding of SMC plasticity through the identification of growth factors and signals that can influence the SMC phenotype, how these regulate SMC plasticity remains unknown. To date, several key transcription factors and regulatory cis elements have been identified that play a role in modulating SMC state. The frontier in understanding the molecular mechanisms underlying SMC plasticity has now advanced to the level of epigenetics. This review will summarize the epigenetic regulation of SMC, highlighting the role of histone modification, DNA methylation, and our most recent identification of a DNA demethylation pathway in SMC that is pivotal in the regulation of the SMC phenotypic state. Many disorders are associated with smooth muscle dysfunction, including atherosclerosis, the major underlying cause of stroke and coronary heart disease, as well as transplant vasculopathy, aneurysm, asthma, hypertension, and cancer. An increased understanding of the major regulators of SMC plasticity will lead to the identification of novel target molecules that may, in turn, lead to novel drug discoveries for the treatment of these diseases. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.

KEYWORDS:

Chromatin; DNA methylation; Epigenetics; Smooth muscle phenotype; TET2; Transcription

PMID:
24937434
PMCID:
PMC4552189
DOI:
10.1016/j.bbagrm.2014.06.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center