Song Ziguang, Zhong Xiao, Li Mingyang, Gao Pingping, Ning Zhongping, Sun Zhiqi, Song Xiang
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Cardiovascular Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
Front Cardiovasc Med. 2021 Oct 12;8:721814. doi: 10.3389/fcvm.2021.721814. eCollection 2021.
High levels of free fatty acids (FFA) are closely associated with obesity and the development of cardiovascular diseases. Recently, nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a potential target for several modern diseases including diabetes. Herein, we explored the underlying mechanisms of NAD metabolism associated with the risk of cardiovascular disease. Our study found that nicotinamide N-methyltransferase (NNMT) mRNA levels were significantly increased in the hearts of FFA-bound-albumin-overloaded mice and in H9C2 cells treated with palmitic acid (PA). We studied the mechanisms underlining the anti-inflammatory and anti-oxidant activities of 1-methylnicotinamide (1-MNA), a metabolite of NNMT. We found a significantly higher level of reactive oxygen species, inflammation, apoptosis, and cell hypertrophy in PA-treated H9C2 cells and this effect was inhibited by 1-MNA treatment. , 1-MNA improved inflammation, apoptosis, and fibrosis damage in mice and this inhibition was associated with inhibited NF-κB activity. In conclusion, our study revealed that 1-MNA may prevent high fatty diet and PA-induced heart injury by regulating Nrf2 and NF-κB pathways.
高水平的游离脂肪酸（FFA）与肥胖和心血管疾病的发展密切相关。最近，烟酰胺腺嘌呤二核苷酸（NAD）代谢已成为包括糖尿病在内的几种现代疾病的潜在靶点。在此，我们探讨了与心血管疾病风险相关的NAD代谢的潜在机制。我们的研究发现，在游离脂肪酸结合白蛋白过载小鼠的心脏以及用棕榈酸（PA）处理的H9C2细胞中，烟酰胺N-甲基转移酶（NNMT）的mRNA水平显著升高。我们研究了NNMT的代谢产物1-甲基烟酰胺（1-MNA）的抗炎和抗氧化活性的潜在机制。我们发现，在PA处理的H9C2细胞中，活性氧、炎症、细胞凋亡和细胞肥大水平显著更高，而1-MNA处理可抑制这种效应。此外，1-MNA改善了小鼠的炎症、细胞凋亡和纤维化损伤，这种抑制作用与NF-κB活性的抑制有关。总之，我们的研究表明，1-MNA可能通过调节Nrf2和NF-κB途径预防高脂肪饮食和PA诱导的心脏损伤。
