Warfarin Accelerates Aortic Calcification by Upregulating Senescence-Associated Secretory Phenotype Maker Expression
Open accessAbstract
Warfarin, a vitamin K antagonist (VKA), is known to promote arterial calcification (AC). In the present study, we conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA); 6655 participants were included. From MESA data, we found that AC was related to both age and vitamin K; furthermore, the score of AC increased with SASP marker including interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) rising. Next, a total of 79 warfarin users in our center developed significantly more calcified coronary plaques as compared to non-VKA users. We investigated the role of warfarin in phosphate-induced AC in different ages by in vitro experimental study. Furthermore, dose-time-response of warfarin was positively correlated with AC score distribution and plasma levels of the SASP maker IL-6 among patients < 65 years, but not among patients ≥ 65 years. In addition, in vitro research suggested that warfarin treatment tended to deteriorate calcification in young VSMC at the early stage of calcification. Our results suggested that aging and warfarin-treatment were independently related to increased AC. Younger patients were more sensitive to warfarin-related AC than older patients, which was possibly due to accumulated warfarin-induced cellular senescence.
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Warfarin, a vitamin K antagonist, induces chronic low-grade inflammation in non-senescent vascular smooth muscle cells and enhances vascular aging and calcification, especially in young patients (<65 years old).
“Accordingly, warfarin, a vitamin K antagonist, has been found to induce chronic low-grade inflammation in non-senescent vascular smooth muscle cells and enhance vascular aging and calcification, especially in young patients (<65 years old) [139,140].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [139]
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
- Authors
- Wei, N., Lu, L., Zhang, H., Gao, M., Ghosh, S., Liu, Z., Qi, J., Wang, J., Chen, J., & Huang, H.
- Affiliations
- Sun Yat-sen University (CN)
- Guangzhou Women and Children Medical Center (CN)
- Corresponding author
- Huang, Hui
- ORCID
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2020-10-22
- Volume
- 2020
- Pages
- 1-13
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC7603623
- OpenAlex
- W3094125425
- Cited by
- 11
- References
- 38
- Citations by year
- 2026: 1 · 2024: 4 · 2022: 5 · 2021: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Public Health Scientific Research Project in Futian District, Shenzhen City (FTWS2019003, JCYJ20190808102005602, JCYJ20180306174648342, 2014A030313035, 20201062, 81500563, 81422011, 81670676, 81870506)
- Basic Research Project of Shenzhen Science and Technology Innovation Committee (FTWS2019003, JCYJ20190808102005602, JCYJ20180306174648342, 2014A030313035, 20201062, 81500563, 81422011, 81670676, 81870506)
- Natural Science Foundation of Guangdong Province (FTWS2019003, JCYJ20190808102005602, JCYJ20180306174648342, 2014A030313035, 20201062, 81500563, 81422011, 81670676, 81870506)
- Traditional Chinese Medicine Bureau of Guangdong Province (FTWS2019003, JCYJ20190808102005602, JCYJ20180306174648342, 2014A030313035, 20201062, 81500563, 81422011, 81670676, 81870506)
- National Natural Science Foundation of China (FTWS2019003, JCYJ20190808102005602, JCYJ20180306174648342, 2014A030313035, 20201062, 81500563, 81422011, 81670676, 81870506)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- warfarin, aortic calcification, arterial calcification, senescence-associated secretory phenotype, cellular senescence, vitamin K antagonists, interleukin-6, TNF-α, vascular smooth muscle cells, phosphate-induced calcification, aging
- MeSH terms
- Abdomen, Aged, Animals, Aortic Valve, Atrial Fibrillation, Dose-Response Relationship, Drug, Electrocardiography, Factor Analysis, Statistical, Female, Humans, Male, Middle Aged, Phosphates, Risk Factors, Time Factors, Vitamin K, Warfarin, Biomarkers, Interleukin-6, Up-Regulation, Multivariate Analysis, Logistic Models, Cellular Senescence, Rats, Sprague-Dawley, Vascular Calcification
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