Association of FOXO3A with right ventricular myocardial fibrosis and its detection by speckle-tracking echocardiography in pulmonary hypertension |
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| Authors: | Rui Song MM Ping Wang MM Lianji Yang MM Juan Liu MM Zhuo Chen MM Yunchuan Ding MB |
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| Affiliation: | 1. Department of Ultrasound, Yan 'an Hospital Affiliated to Kunming Medical University, Key Laboratory of Cardiovascular Disease of Yunnan province, Kunming, China Department of Ultrasound, Second Affiliated Hospital of Kunming Medical University, Kunming, China;2. Department of Ultrasound, Yan 'an Hospital Affiliated to Kunming Medical University, Key Laboratory of Cardiovascular Disease of Yunnan province, Kunming, China;3. Department of Cardiology, Second Affiliated Hospital of Kunming Medical University, Kunming, China;4. Department of Ultrasound, Second Affiliated Hospital of Kunming Medical University, Kunming, China |
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| Abstract: | Background Myocardial fibrosis can result in right ventricular (RV) dysfunction, a critical factor in poor clinical outcomes and high mortality rates among patients with pulmonary hypertension (PH). Decreased RV myocardial strain rates have been reported in PH patients. The expression of FOXO3A may play a crucial role in myocardial fibrosis; however, the relationship between myocardial fibrosis, speckle-tracking echocardiography (STE), and the transcription factor FOXO3A remains unclear. This study aimed to explore the relationship between the molecular mechanisms of myocardial fibrosis and noninvasive ultrasound evaluation indices to provide a reliable molecular foundation for the early diagnosis of right heart dysfunction in clinical settings. Methods A progressive right heart failure (RHF) rat model was established through subcutaneous injections of monocrotaline. Rats were divided into baseline, 2-week, 4-week, and 6-week groups based on the disease course. RV structure, function, and myocardial strain were assessed via echocardiography. Myocardial fibrosis severity was determined using PSR staining. The correlation between myocardial strain and RV myocardial fibrosis was analyzed. FOXO3A, collagen I, collagen III, and BNP expressions were tested using western blotting. Results As the disease progressed, the right ventricle significantly expanded, and the RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), RV global longitudinal strain (RVLS global), and RV free wall longitudinal strain (RVLS FW) gradually declined. However, the reductions in RVLS global and RVLS FW occurred earlier than that of RVFAC, TAPSE. Significant correlations were observed between RVLS global, RVLS FW, and collagen deposition. FOXO3A expression gradually decreased with disease progression, while BNP, collagen I, and collagen III expressions gradually increased. Conclusions Decreases in RVLS global and RVLS FW in RHF rats occurred earlier than RVFAC and were associated with RV myocardial fibrosis. Furthermore, FOXO3A may have a protective role in the process of RV myocardial fibrosis. |
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| Keywords: | FOXO3A transcription factor myocardial fibrosis myocardial strain pulmonary hypertension right ventricular dysfunction speckle-tracking echocardiography |
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