Year: 2024
Type: article
Abstract: Vascular smooth muscle cells (VSMCs) in adult arteries maintain substantial phenotypic plasticity, which allows for the reversible cell state changes that enable vascular remodelling and homeostasis. In atherosclerosis, VSMCs dedifferentiate in response to lipid accumulation and inflammation, resulting in loss of their characteristic contractile state. Recent studies showed that individual, pre-existing VSMCs expand clonally and can acquire many different phenotypes in atherosclerotic lesions. The changes in gene expression underlying this phenotypic diversity are mediated by epigenetic modifications which affect transcription factor access and thereby gene expression dynamics. Additionally, epigenetic mechanisms can maintain cellular memory, potentially facilitating reversion to the contractile state. While technological advances have provided some insight, a comprehensive understanding of how VSMC phenotypes are governed in disease remains elusive. Here we review current literature in light of novel insight from studies at single-cell resolution. We also discuss how lessons from epigenetic studies of cellular regulation in other fields could help in translating the potential of targeting VSMC phenotype conversion into novel therapies in cardiovascular disease.
Source: Atherosclerosis
Authors: Jordi Lambert, Helle F. Jørgensen
Institution: University of Cambridge
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,790
Funders: British Heart Foundation, Novo Nordisk
Awards: Intercellular communication pathways in atherosclerosis and plaque destabilisation (PLAK TALK) (joint funding with DZHK and DHF), Research Excellence (round 3), From genetic association to function: the role of coronary artery disease-associated genetic variants in the control of vascular smooth muscle cell plasticity, G5408067991
OpenAlex ID: W4405237743