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

Abstract EN

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.