Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Cell Cycle. 2021 Nov;20(21):2278-2290. doi: 10.1080/15384101.2021.1981631. Epub 2021 Sep 29.
Cathelicidin-WA (CWA) is a novel cathelicidin peptide isolated from snakes that has been suggested to exert anti-inflammatory effects. The aim of our study was to investigate whether cathelicidin-WA (CWA) could protect the heart from diabetic cardiomyopathy (DCM). Streptozotocin (STZ) injection was used to establish a mouse model of DCM. CWA peptide (2 mg/kg or 8 mg/kg) was continuously administered to the mice from 10 weeks to 16 weeks after STZ injection. The mice in the DCM group exhibited cardiac dysfunction, while 8 mg/kg CWA ameliorated this cardiac dysfunction. Cardiac fibrosis, inflammation, and oxidative stress as well as cardiomyocyte apoptosis in the DCM mice were decreased by treatment with 8 mg/kg CWA. We isolated neonatal rat cardiomyocytes and stimulated the cells with high glucose to establish an in vitro model of myocyte cell injury. Consistently, CWA inhibited high glucose-induced cell death, inflammation and oxidative stress in the myocytes. Moreover, CWA reduced the formation of the NLR family pyrin domain-containing 3 (NRLP3) inflammasome by regulating thioredoxin-interacting protein expression and p65 activation. NLRP3 overexpression inhibited the beneficial effects of CWA on the heart during DCM and on high glucose-induced myocyte injury. In summary, CWA attenuates cardiac injury and preserves cardiac function during DCM by targeting the NLRP3 pathway.: AAV9: Adeno associated virus; AGE: Advanced Glycation End products; CWA: Cathelicidin-WA; DCM: diabetic cardiomyopathy; Gpx: glutathione peroxidase; HG: high glucose; IL: Interleukin; NLR: Family Pyrin Domain Containing 3 (NRLP3); TXNIP: Thioredoxin interacting protein; LVEF: left ventricular ejection fraction; MDA: Malondialdehyde; MnSOD: manganese superoxide dismutase; NADPH: Nicotinamide adenine dinucleotide phosphate; NAC: N-acetyl-cysteine; NRCMs: Neonatal rat cardiomyocytes; ROS: reactive oxygen species; STZ: Streptozotocin; TNFa: tumor necrosis factor a.
抗菌肽-WA（CWA）是一种从蛇中分离出来的新型抗菌肽，据报道具有抗炎作用。我们的研究旨在探讨抗菌肽-WA（CWA）是否可以保护心脏免受糖尿病心肌病（DCM）的影响。链脲佐菌素（STZ）注射用于建立 DCM 小鼠模型。从 STZ 注射后 10 周到 16 周，连续给予 CWA 肽（2 mg/kg 或 8 mg/kg）。DCM 组小鼠表现出心脏功能障碍，而 8 mg/kg CWA 改善了这种心脏功能障碍。CWA 处理降低了 DCM 小鼠的心肌纤维化、炎症和氧化应激以及心肌细胞凋亡。我们分离新生大鼠心肌细胞并以高葡萄糖刺激细胞，建立心肌细胞损伤的体外模型。一致地，CWA 抑制了高葡萄糖诱导的心肌细胞死亡、炎症和氧化应激。此外，CWA 通过调节硫氧还蛋白相互作用蛋白表达和 p65 激活来减少 NOD、LRP 和 caspase-1 家族包含 pyrin 域 3（NLRP3）炎性小体的形成。NLRP3 过表达抑制了 CWA 在 DCM 期间和高葡萄糖诱导的心肌细胞损伤中对心脏的有益作用。总之，CWA 通过靶向 NLRP3 途径减轻 DCM 期间的心脏损伤并保持心脏功能。
