Open Access

ARTICLE

Exploration of the Notch3‐HES5 signal pathway in monocrotaline‐induced pulmonary hypertension using rat model

Xing Chen, Wu Zhou, Qinghua Hu, Lingjin Huang

Department of Cardiothoracic Surgery, Xiangya Hospital Central South University, Changsha, P.R. China

* Corresponding Author: Lingjin Huang, Department of Cardiothoracic Surgery, Xiangya Hospital Central South University, Changsha 410008, P.R. China. Email:

Congenital Heart Disease 2019, 14(3), 396-402. https://doi.org/10.1111/chd.12733

Abstract

Objective: This study explores the role of the Notch3‐HES5 signal pathway in mono‐ crotaline‐induced pulmonary hypertension (PH) using rat models.
Method: Sprague Dawley rats (n = 45) were randomly grouped into normal group, control group, and model group. Rats in the model group were used to establish the PH rat model. Four weeks after model establishment, right catheterization was used to measure the mean pulmonary arterial pressure (mPAP) and right ventricular sys‐ tolic pressure (RVSP) to analyze hemodynamic changes. The severity of PH was as‐ sessed by the right ventricular hypertrophy index (RVHI) and percentage of media thickness (MT%). The expressions of Notch3 and HES5 were determined by ELISA and reverse transcription‐polymerase chain reaction. The correlation of mRNA ex‐ pressions of Notch3 and HES5 with mPAP was analyzed.
Results: Rats in the model group had higher mPAP, RVSP, RVHI, and MT% as well as thicker pulmonary arterioles wall than those in the normal group. Immunohistochemistry showed Notch3 and HES5 were mainly expressed in the smooth muscle cell in pul‐ monary arterioles. In comparison with the normal group, rats in the model group had elevated expressions of Notch3 and HES5. The mean pulmonary arterial pressure was positively related with mRNA expressions of Notch3 and HES5.
Conclusion: Taken together, our study demonstrates that monocrotaline‐induced PH rats had high expressions of the Notch3‐HES5 signal pathway in the pulmonary arte‐ rioles. The signal of the Notch3‐HES5 signal pathway was positively related to the hemodynamics of the lung vasculature.

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