School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510699, China.
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510699, China.
Eur J Pharmacol. 2023 Sep 5;954:175849. doi: 10.1016/j.ejphar.2023.175849. Epub 2023 Jun 16.
Short-chain acyl-CoA dehydrogenase (SCAD), the rate-limiting enzyme for fatty acid β-oxidation, has a negative regulatory effect on pathological cardiac hypertrophy and fibrosis. FAD, a coenzyme of SCAD, participates in the electron transfer of SCAD-catalyzed fatty acid β-oxidation, which plays a crucial role in maintaining the balance of myocardial energy metabolism. Insufficient riboflavin intake can lead to symptoms similar to short-chain acyl-CoA dehydrogenase (SCAD) deficiency or flavin adenine dinucleotide (FAD) gene abnormality, which can be alleviated by riboflavin supplementation. However, whether riboflavin can inhibit pathological cardiac hypertrophy and fibrosis remains unclear. Therefore, we observed the effect of riboflavin on pathological cardiac hypertrophy and fibrosis. In vitro experiments, riboflavin increased SCAD expression and the content of ATP, decreased the free fatty acids content and improved PE-induced cardiomyocytes hypertrophy and AngⅡ-induced cardiac fibroblasts proliferation by increasing the content of FAD, which were attenuated by knocking down the expression of SCAD using small interfering RNA. In vivo experiments, riboflavin significantly increased the expression of SCAD and the energy metabolism of the heart to improve TAC induced pathological myocardial hypertrophy and fibrosis in mice. The results demonstrate that riboflavin improves pathological cardiac hypertrophy and fibrosis by increasing the content of FAD to activate SCAD, which may be a new strategy for treating pathological cardiac hypertrophy and fibrosis.
短链酰基辅酶 A 脱氢酶（SCAD）是脂肪酸β氧化的限速酶，对病理性心肌肥厚和纤维化有负向调节作用。FAD 是 SCAD 的辅酶，参与 SCAD 催化的脂肪酸β氧化的电子传递，对维持心肌能量代谢平衡起着至关重要的作用。核黄素摄入不足可导致类似于短链酰基辅酶 A 脱氢酶（SCAD）缺乏或黄素腺嘌呤二核苷酸（FAD）基因异常的症状，这些症状可通过核黄素补充来缓解。然而，核黄素是否能抑制病理性心肌肥厚和纤维化尚不清楚。因此，我们观察了核黄素对病理性心肌肥厚和纤维化的影响。体外实验表明，核黄素通过增加 FAD 的含量，增加 SCAD 的表达和 ATP 的含量，降低游离脂肪酸的含量，改善 PE 诱导的心肌细胞肥大和 AngⅡ诱导的心肌成纤维细胞增殖，而使用小干扰 RNA 敲低 SCAD 的表达可减弱这种作用。体内实验表明，核黄素显著增加了 SCAD 的表达和心脏的能量代谢，从而改善了 TAC 诱导的小鼠病理性心肌肥厚和纤维化。结果表明，核黄素通过增加 FAD 的含量来激活 SCAD，从而改善病理性心肌肥厚和纤维化，这可能是治疗病理性心肌肥厚和纤维化的一种新策略。
