Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition

Summary:

During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. The authors of this article, led by GCIR member Prof. Marie-Luce Bochaton-Piallat, previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. They investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. They found apelin was highly expressed in R-SMCs compared with S-SMCs. They observed a nuclear expression of apelin in SMCs within experimentally induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localisation of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest apelin acts via nuclear re-localisation of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.

This work has been funded by the Swiss National Science Foundation and the Novartis Foundation for Medical-Biological Research.

Full article: https://www.nature.com/articles/s41598-023-45470-z

Why is it important?

Cardiovascular diseases are the leading cause of death worldwide, responsible for 32% of all global deaths, with approximately 17.9 million people dying from them in 2019. Atherosclerosis is a primary cause of vascular disease, which occurs when fats, cholesterol, and other substances accumulate in and on the artery walls, forming plaque that can narrow the arteries and block blood flow. The arterial wall's medial layer consists mostly of vascular smooth muscle cells (SMCs). These cells are responsible for regulating vascular tone by assuming a contractile phenotype, they are able to stretch or relax. This phenotypic switching plays a significant role in the development of atherosclerosis. In this study, Prof. Marie-Luce Bochaton-Piallat's team explained how apelin, a previously known vasoconstrictor, affects SMC phenotypic transition by regulating the expression and localisation of protein S100A4. Apelin might constitute a potential pharmacological target in toning down SMC-driven atherosclerosis development.

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