Yan Xiaoliang, Wu Lin, Gao Min, Yang Pengjie, Yang Jinjing, Deng Yongzhi
Department of Cardiothoracic Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Department of Cardiology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, Zhejiang 317500, P.R. China.
Exp Ther Med. 2022 Apr;23(4):292. doi: 10.3892/etm.2022.11222. Epub 2022 Feb 17.
The recently identified adipocytokine omentin was previously found to be expressed mainly in human omental and visceral adipose tissues. As such, reduced plasma concentrations of omentin were revealed to be associated with increased risks of cardiovascular diseases. Omentin has also been previously demonstrated to exert anti-inflammatory effects. By contrast, resistin is a protein that has been associated with obesity and type-2 diabetes mellitus, and the serum concentration of resistin is increased significantly in these populations. Resistin is involved in mediating inflammation development, where they can promote cardiac hypertrophy in humans through toll-like receptor 4 (TLR4)-related signaling. In the present study, the potential effects of omentin on resistin-induced hypertrophy in H9c2 cardiomyoblasts were investigated. In the absence/presence of omentin, H9c2 cardiomyoblasts were treated with resistin. Omentin was found to significantly inhibit resistin-induced increases in the surface area of H9c2 cardiomyoblasts as determined by immunofluorescence. In addition, omentin significantly inhibited resistin-induced increases in the mRNA expression of atrial natriuretic factor, brain natriuretic peptide, β-myosin heavy chain (which is a characteristic feature of cardiac hypertrophy) and TLR4, which was determined using reverse-transcription-quantitative PCR. According to western blotting results, omentin significantly inhibited resistin-induced ERK phosphorylation, which is an important mediator of cardiomyoblast hypertrophy. Furthermore, omentin significantly inhibited resistin-induced protein expression of TLR4, myeloid differentiation factor 88 (MyD88) and NF-κB phosphorylation, both of which are important members of inflammatory signaling. To conclude, data from the present study suggest that omentin can inhibit resistin-induced H9c2 cardiomyoblast hypertrophy through inhibition of the TLR4/MyD88/NF-κB signaling pathway. Therefore, omentin serve as an attractive therapeutic target against resistin-induced cardiac hypertrophy.
最近发现的脂肪细胞因子网膜素，此前被发现主要在人体网膜和内脏脂肪组织中表达。因此，血浆网膜素浓度降低与心血管疾病风险增加有关。网膜素此前也已被证明具有抗炎作用。相比之下，抵抗素是一种与肥胖和2型糖尿病相关的蛋白质，在这些人群中抵抗素的血清浓度显著升高。抵抗素参与介导炎症发展，它可以通过Toll样受体4（TLR4）相关信号通路促进人类心肌肥大。在本研究中，研究了网膜素对抵抗素诱导的H9c2心肌成纤维细胞肥大的潜在影响。在有无网膜素的情况下，用抵抗素处理H9c2心肌成纤维细胞。通过免疫荧光测定发现，网膜素能显著抑制抵抗素诱导的H9c2心肌成纤维细胞表面积增加。此外，网膜素显著抑制抵抗素诱导的心房利钠因子、脑利钠肽、β-肌球蛋白重链（这是心肌肥大的一个特征）和TLR4的mRNA表达增加，这是用逆转录定量PCR测定的。根据蛋白质印迹结果，网膜素显著抑制抵抗素诱导的ERK磷酸化，ERK是心肌成纤维细胞肥大的重要介质。此外，网膜素显著抑制抵抗素诱导的TLR4、髓样分化因子88（MyD88）蛋白表达和NF-κB磷酸化，二者都是炎症信号的重要成员。总之，本研究数据表明，网膜素可通过抑制TLR4/MyD88/NF-κB信号通路来抑制抵抗素诱导的H9c2心肌成纤维细胞肥大。因此，网膜素是抵抗素诱导的心肌肥大的一个有吸引力的治疗靶点。
