Association of FOXO3A with Right Ventricular Myocardial Fibrosis and its Speckle-tracking Echocardiographic Detecting in Pulmonary Hypertension： An animal study

Abstract

Background Myocardial fibrosis may lead to right ventricular (RV) dysfunction, which is a key determinant to poor clinical prognosis and high mortality in patients with pulmonary hypertension (PH). Reduced right ventricular myocardial strain rate was reported in PH patients. The expression of FOXO3A may have an essential role in myocardial fibrosis. However, the relationship between myocardial fibrosis and speckle-tracking echocardiography (STE) or transcription factor FOXO3A is unclear. Therefore, we aimed to exploring the relationship between the molecular mechanism of myocardial fibrosis and the noninvasive ultrasound evaluation index in order to provide a reliable molecular basis for the early diagnosis of right heart dysfunction in clinic. Methods Progressive right heart failure (RHF) rat model was established by subcutaneous injection of monocrotaline. Rats divided into baseline, 2-week, 4-week and 6-week according to the course of disease. Right ventricular structure, function and myocardial strain were determined via echocardiography. The degree of myocardial fibrosis was determined by PSR staining. The correlation of myocardial strain to RV myocardial fibrosis was analyzed. The expression of FOXO3A, collagen I, collagen III and BNP were test via western blotting. Results As the disease progresses, the right ventricle significantly expands, RV fractional area change (FAC), RV global longitudinal strain (RVLS global) and RV free wall longitudinal strain (RVLS FW) gradually decreases. While the reduction of RVLS global, RVLS FW appeared earlier than that of RVFAC. Significant correlations were observed between RVLS global, RVLS FW and collagen deposition. FOXO3A expression gradually decreased with the disease progression, while the expression of BNP, collagen I, collagen III gradually increased. Conclusions Decreased of RVLS global, RVLS FW in RHF rats are happened earlier than RVFAC, and have associated with RV myocardial fibrosis. While, FOXO3A may plays a protective role in the process of RV myocardial fibrosis.