Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Qianru Zhang; Jiawen Ye; Gan Yang; Ling Yang; Zhongli Chen; Ke Yang; Jia Teng Sun; Yan Liu

doi:10.3389/fcvm.2022.1050310

Frontiers in Cardiovascular Medicine (Jan 2023)

Role of follistatin-like 1 levels and functions in calcific aortic stenosis

Qianru Zhang,
Jiawen Ye,
Gan Yang,
Ling Yang,
Zhongli Chen,
Ke Yang,
Jia Teng Sun,
Yan Liu

Affiliations

Qianru Zhang: Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jiawen Ye: Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Gan Yang: Department of Cardiology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
Ling Yang: Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhongli Chen: State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Ke Yang: Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jia Teng Sun: Department of Cardiology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
Yan Liu: Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

DOI: https://doi.org/10.3389/fcvm.2022.1050310
Journal volume & issue: Vol. 9

Abstract

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BackgroundCalcific aortic valve disease (CAVD) is a progressive disease resulting in severe calcific aortic stenosis (AS), and there is increasing interest in the discovery of novel biomarkers to identify patients with potential future calcific AS at an early stage. This study aimed to determine whether follistatin-like 1 (FSTL1) is associated with calcific AS events and its exact role in aortic valve calcification.MethodsA prospective observational cohort study involving 656 patients was performed to investigate the relationship between serum FSTL1 and calcific AS incidence during a follow-up of 5 years. Furthermore, we detected FSTL1 levels in valvular interstitial cells (VICs) from calcified valves and explored the effects of FSTL1 on VIC osteogenic differentiation in vitro as well as the signaling pathways involved.ResultsDuring a median follow-up of 5 years, lower FSTL1 levels were associated with a significantly higher risk of calcific AS events (log rank test, P = 0.007). In addition, Cox multivariable regression analyses verified the predictive value of FSTL1 after adjusting for both demographic features and laboratory confounders. Consistent with our results for serum, a lower concentration of FSTL1 was observed in calcified human valves (n = 11) and mainly colocalized with VICs. Recombinant human FSTL1 (rhFSTL1) stimulation inhibited calcium deposition, alkaline phosphatase (ALP) activity, and osteogenic gene expression partly through the downregulation of the ERK1/2 pathway.ConclusionTaken together, this study provides a strong rationale to consider FSTL1 as a potential therapeutic target for calcific AS.

Published in Frontiers in Cardiovascular Medicine

ISSN: 2297-055X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.frontiersin.org/journals/cardiovascular-medicine

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