Department of Cardiology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia Baotou Medical University, Baotou, Inner Mongolia 014010, China.
Biochem Cell Biol. 2022 Apr;100(2):93-103. doi: 10.1139/bcb-2019-0450. Epub 2020 Nov 27.
Metabolic remodeling in heart failure (HF) is a type of overload cardiomyopathy caused by insufficient energy supply or an imbalance of glucose and lipid metabolism. Therefore, metabolic pathways may serve as potential targets for HF treatment. BRM-associated factor (BAF) 60c (also known as smarcd3) promotes the transformation of oxidative muscle fibers to glycolytic muscle fibers. Our study aimed to test whether BAF60c and the PGC1α-PPARα-mTOR pathway interact to affect myocardial metabolism in HF rats. Established rat models of HF were injected with BAF60c low or overexpression plasmids to assess cardiac contractile proteins, energy metabolism, oxidative metabolism, glycolysis, high-energy phosphate content, mitochondrial function, and apoptosis. BAF60c overexpression/siRNA plasmid was transfected into H9C2 cells. These results suggest that HF rats present decreased levels of BAF60c, increased glycolysis, and reduced levels of cardiac contractile proteins, PGC1α, PPARα, and oxidative metabolism. Overexpression of BAF60c maintained the balance between oxidative metabolism and glycolysis and activated the PGC1α-PPARα-mTOR pathway. PGC1α interacted with BAF60c, and overexpression of PGC1α decreased BAF60c knockdown, damaging H9C2 cells. Collectively, overexpression of BAF60c activated the PGC1α-PPARα-mTOR pathway, maintained the oxidative metabolism/glycolysis balance, and improved mitochondrial function in HF rats. This study offers novel insights into HF treatment.
心力衰竭（HF）中的代谢重塑是一种由能量供应不足或葡萄糖和脂质代谢失衡引起的过载性心肌病。因此，代谢途径可能成为 HF 治疗的潜在靶点。BRM 相关因子（BAF）60c（也称为 smarcd3）促进氧化型肌纤维向糖酵解型肌纤维的转化。我们的研究旨在测试 BAF60c 是否与 PGC1α-PPARα-mTOR 途径相互作用，以影响 HF 大鼠的心肌代谢。用 BAF60c 低表达或过表达质粒注射建立 HF 大鼠模型，以评估心肌收缩蛋白、能量代谢、氧化代谢、糖酵解、高能磷酸含量、线粒体功能和细胞凋亡。将 BAF60c 过表达/siRNA 质粒转染到 H9C2 细胞中。结果表明，HF 大鼠的 BAF60c 水平降低，糖酵解增加，心肌收缩蛋白、PGC1α、PPARα 和氧化代谢水平降低。BAF60c 的过表达维持了氧化代谢和糖酵解之间的平衡，并激活了 PGC1α-PPARα-mTOR 途径。PGC1α 与 BAF60c 相互作用，过表达 PGC1α 降低了 BAF60c 敲低，从而损害 H9C2 细胞。综上所述，BAF60c 的过表达激活了 PGC1α-PPARα-mTOR 途径，维持了 HF 大鼠氧化代谢/糖酵解的平衡，改善了线粒体功能。这项研究为 HF 的治疗提供了新的思路。
