PPAR-α regulates metabolic remodelling and participates in myocardial fibrosis in patients with atrial fibrillation of rheumatic heart disease

Introduction: This study will explore the correlation of peroxisome proliferator activated receptor-alpha (PPAR-alpha) regulation of metabolic remodelling in the myocardial fibrosis of atrial fibrillation (AF) in rheumatic heart disease. Material and methods: The left atrial appendage tissues were evaluated by Masson staining for fibrosis degree, and Western Blot was used to detect the expression of proteins related to glucose metabolism disorder, lipid metabolism abnormality, and mitochondrial dysfunction. The myocardial fibroblasts were established by stimulation with ANG II, and the PPAR-alpha agonist GW7647 was administered. The changes of phenotype transformation of myocardial fibroblasts were detected by cellular immunofluorescence, the secretion level of supernatant collagen was detected by ELISA. Finally, the correlation between PPAR-alpha protein expression and myocardial fibrosis was analysed and a conclusion was drawn. Results: Masson staining showed that the degree of myocardial fibrosis in patients with AF was significantly increased; WB analysis showed that there were statistically significant differences in protein expression related to glucose metabolism disorder, lipid metabolism abnormality, and mitochondrial dysfunction. There was a correlation between PPAR-alpha protein expression and myocardial fibrosis (r = -0.5322, p < 0.0001). After stimulation with PPAR-alpha agonist GW7647, the phenotypic differentiation of myocardial fibro-blasts into myofibroblasts was inhibited. The protein expression related to mitochondrial dysfunction was statistically different. Conclusions: This study found that there is a negative correlation between the expression of PPAR-alpha protein and myocardial fibrosis in rheumatic heart disease AF, which plays a protective role. PPAR-alpha may participate in the pathogenesis of myocardial fibrosis in rheumatic heart disease AF by regulating glucose metabolism, lipid metabolism, and mitochondrial function.