Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition
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Abstract
During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We 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 localization 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 that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.
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The cardioprotective effects of Apelin partly depend on endothelial cell signaling in skeletal muscle and adipose tissue, providing a molecular connection point for the exercise-muscle-vascular axis.
“Notably, the cardioprotective effects of Apelin partly depend on endothelial cell signaling in skeletal muscle and adipose tissue, providing a precise molecular connection point for the “exercise-muscle-vascular” axis [64].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [64]
The Introduction says apelin regulates vascular tone through endothelium-dependent nitric oxide production, and the Discussion describes a possible anti-atherogenic role in endothelial cells. Neither section says its cardioprotective effects depend on endothelial signaling in skeletal muscle or adipose tissue, or establishes an exercise–muscle–vascular connection. Our copy provides only the broader vascular link. (LLM, conf=0.82)
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- Authors
- Cardoso Dos Santos, L. M., Azar, P., Brun, C., König, S., Roatti, A., Baertschi, A. J., Chaabane, C., & Bochaton-Piallat, M.-L.
- Affiliations
- University of Geneva (CH)
- ORCID
- Azar, Pascal
- Venue
- Scientific Reports
- Published
- 2023-10-31
- Volume
- 13
- Issue
- 1
- Pages
- 18736-18736
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC10618247
- OpenAlex
- W4388048450
- Cited by
- 9
- References
- 46
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novartis Stiftung für Medizinisch-Biologische Forschung (14C193)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_185370/1)
- Topics
- Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apelin, smooth muscle cells, phenotypic switching, S100A4, intimal thickening, atherosclerosis, nuclear localization, PDGF-BB, coronary arteries, aorta, dedifferentiation
- MeSH terms
- Apelin, Animals, Cell Movement, Cells, Cultured, Phenotype, Swine, Myocytes, Smooth Muscle, Atherosclerosis, Rats
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