Warfarin Accelerates Aortic Calcification by Upregulating Senescence-Associated Secretory Phenotype Maker Expression

Autor: Ningle Wei, Sounak Ghosh, Junhua Qi, Huanji Zhang, Hui Huang, Jingfeng Wang, Liuyi Lu, Zhaoyu Liu, Ming Gao, Jie Chen
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Aging
Time Factors
Vitamin K
030204 cardiovascular system & hematology
Biochemistry
Rats
Sprague-Dawley
Electrocardiography
0302 clinical medicine
Risk Factors
Abdomen
Atrial Fibrillation
030212 general & internal medicine
Cellular Senescence
General Medicine
Middle Aged
Vitamin K antagonist
Up-Regulation
Arterial calcification
Dose–response relationship
Aortic Valve
Female
Tumor necrosis factor alpha
Research Article
medicine.drug
medicine.medical_specialty
Article Subject
medicine.drug_class
Aortic calcification
Phosphates
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
cardiovascular diseases
Vascular Calcification
Aged
Dose-Response Relationship
Drug
QH573-671
Interleukin-6
business.industry
Warfarin
Cell Biology
medicine.disease
In vitro
Logistic Models
Endocrinology
Multivariate Analysis
Factor Analysis
Statistical
business
Cytology
Biomarkers
Calcification
Zdroj: Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
Oxidative Medicine and Cellular Longevity
ISSN: 1942-0994
1942-0900
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: