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Volume 26
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10.3390/ijms26178163
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning

by
Corina Cinezan
1,2,*,
Dan Claudiu Magureanu
3,4,*,
Maria Luiza Hiceag
5,6,
Camelia Bianca Rus
1,2,7,
Ioana Tiberia Ilias
1,2,
Iulia Denisa Bogdan
1,2,7,
Alexandra Manuela Buzle
1,2,7 and
Angela Cozma
8
1
Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
2
Clinical County Emergency Hospital Bihor, 410169 Oradea, Romania
3
Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 40337 Cluj-Napoca, Romania
4
Cardiology Department, Niculae Stancioiu Heart Institute, 400001 Cluj-Napoca, Romania
5
Cardiology Department, Rehabilitation Hospital, 400347 Cluj-Napoca, Romania
6
Cardiology Department, Municipal Hospital Aiud, 515200 Aiud, Romania
7
Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
8
4th Department of Internal Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(17), 8163; https://doi.org/10.3390/ijms26178163
Submission received: 17 July 2025 / Revised: 18 August 2025 / Accepted: 20 August 2025 / Published: 22 August 2025
(This article belongs to the Special Issue New Trends in Diabetes, Hypertension and Cardiovascular Diseases: 3rd Edition)
Versions Notes

Abstract

Aortic stenosis (AS) and atherosclerosis are progressive cardiovascular conditions that frequently coexist and share multiple clinical and molecular features. Medical therapies have shown effectiveness in preventing and treating atherosclerosis and its consequences. For AS, effective pharmacological therapies remain limited. Understanding the shared risk factors and mechanisms between the two conditions may provide opportunities for therapeutic repositioning in AS. We performed a narrative review focusing on studies published from 2005 to 2025. Inclusion criteria encompassed clinical trials, experimental models, and molecular studies addressing overlapping risk factors, pathological pathways, and treatment approaches for AS and atherosclerosis. AS and atherosclerosis share key risk factors, including age, hypertension, hyperlipidemia, and diabetes. Molecular mechanisms, such as chronic inflammation, endothelial dysfunction, oxidative stress, lipid accumulation, and calcific remodeling, are common to both. Pathways involving the renin-angiotensin system, Notch signaling, and osteogenic mediators contribute to disease progression. Several drug classes, notably proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipoprotein(a) (Lp(a)) lowering therapies, anti-inflammatory agents, and immunomodulators, show potential for repositioning in AS management. The substantial overlap in risk factors and molecular mechanisms between AS and atherosclerosis supports a rationale for therapeutic repositioning. Targeting shared pathways could lead to innovative strategies for slowing AS progression and improving patient outcomes.
Keywords: aortic stenosis; atherosclerosis; risk factors; mechanism; PCSK 9 inhibitors; lipoprotein(a); DPP-4 inhibitors; denosumab; therapeutic repositioning aortic stenosis; atherosclerosis; risk factors; mechanism; PCSK 9 inhibitors; lipoprotein(a); DPP-4 inhibitors; denosumab; therapeutic repositioning

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MDPI and ACS Style

Cinezan, C.; Magureanu, D.C.; Hiceag, M.L.; Rus, C.B.; Ilias, I.T.; Bogdan, I.D.; Buzle, A.M.; Cozma, A. Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning. Int. J. Mol. Sci. 2025, 26, 8163. https://doi.org/10.3390/ijms26178163

AMA Style

Cinezan C, Magureanu DC, Hiceag ML, Rus CB, Ilias IT, Bogdan ID, Buzle AM, Cozma A. Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning. International Journal of Molecular Sciences. 2025; 26(17):8163. https://doi.org/10.3390/ijms26178163

Chicago/Turabian Style

Cinezan, Corina, Dan Claudiu Magureanu, Maria Luiza Hiceag, Camelia Bianca Rus, Ioana Tiberia Ilias, Iulia Denisa Bogdan, Alexandra Manuela Buzle, and Angela Cozma. 2025. "Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning" International Journal of Molecular Sciences 26, no. 17: 8163. https://doi.org/10.3390/ijms26178163

APA Style

Cinezan, C., Magureanu, D. C., Hiceag, M. L., Rus, C. B., Ilias, I. T., Bogdan, I. D., Buzle, A. M., & Cozma, A. (2025). Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning. International Journal of Molecular Sciences, 26(17), 8163. https://doi.org/10.3390/ijms26178163

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