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

Objective This study explores the role of the Notch3-HES5 signal pathway in monocrotaline-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 systolic pressure (RVSP) to analyze hemodynamic changes. The severity of PH was assessed 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 expressions 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 pulmonary 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 arterioles. The signal of the Notch3-HES5 signal pathway was positively related to the hemodynamics of the lung vasculature.