Abnormal mechanical stress on bicuspid aortic valve induces valvular calcification and inhibits Notch1/NICD/Runx2 signal

Guangzhou Li; Na Shen; Huifang Deng; Yixuan Wang; Gangcheng Kong; Jiawei Shi; Nianguo Dong; Cheng Deng

doi:10.7717/peerj.14950

Abnormal mechanical stress on bicuspid aortic valve induces valvular calcification and inhibits Notch1/NICD/Runx2 signal

PeerJ. 2023 Mar 6:11:e14950. doi: 10.7717/peerj.14950. eCollection 2023.

Authors

Guangzhou Li^#¹, Na Shen^#², Huifang Deng¹, Yixuan Wang¹, Gangcheng Kong³, Jiawei Shi¹, Nianguo Dong¹, Cheng Deng¹

Affiliations

¹ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

^# Contributed equally.

Abstract

Background: Bicuspid aortic valve (BAV) is a congenital cardiac deformity, increasing the risk of developing calcific aortic valve disease (CAVD). The disturbance of hemodynamics can induce valvular calcification, but the mechanism has not been fully identified.

Methods: We constructed a finite element model (FEM) of the aortic valve based on the computed tomography angiography (CTA) data from BAV patients and tricuspid aortic valve (TAV) individuals. We analyzed the hemodynamic properties based on our model and investigated the characteristics of mechanical stimuli on BAV. Further, we detected the expression of Notch, NICD and Runx2 in valve samples and identified the association between mechanical stress and the Notch1 signaling pathway.

Results: Finite element analysis showed that at diastole phase, the equivalent stress on the root of BAV was significantly higher than that on the TAV leaflet. Correspondingly, the expression of Notch1 and NICH decreased and the expression of Runx2 elevated significantly on large BAV leaflet belly, which is associated with equivalent stress on leaflet. Our findings indicated that the root of BAV suffered higher mechanical stress due to the abnormal hemodynamic environment, and the disturbance of the Notch1/NICD/Runx2 signaling pathway caused by mechanical stimuli contributed to valvular calcification.

Keywords: Bicuspid aortic valve; Finite element analysis; Mechanical stimuli; Notch1 signaling pathway; Valvular calcification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Valve / abnormalities
Aortic Valve Stenosis* / metabolism
Bicuspid Aortic Valve Disease* / metabolism
Core Binding Factor Alpha 1 Subunit / metabolism
Heart Valve Diseases* / metabolism
Humans
Receptor, Notch1 / metabolism
Stress, Mechanical

Substances

NOTCH1 protein, human
Receptor, Notch1
RUNX2 protein, human
Core Binding Factor Alpha 1 Subunit

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 31500794). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.