高血压是代谢综合征的病理状态,增加心血管疾病的风险。管理高血压具有挑战性,我们旨在确定代谢性高血压(MHR)的致病因素和治疗目标。用高糖联合治疗建立MHR大鼠模型,高脂肪饮食和乙醇。使用苏木精-伊红和天狼星红染色进行组织病理学观察。进行转录组测序以筛选差异表达的基因。泛素特异性蛋白酶18(USP18)在增殖中的作用,凋亡,使用细胞计数试剂盒-8,流式细胞术,和酶联免疫吸附测定。此外,对MHR中的USP18下游信号通路进行了筛选,并通过蛋白质印迹研究了USP18对这些信号通路的影响。在MHR模型中,总胆固醇和低密度脂蛋白水平升高,而高密度脂蛋白水平下降。此外,高血管厚度和胶原蛋白的百分比注意随着丙二醛的增加,降低超氧化物歧化酶和过氧化氢酶水平。染色结果显示,MHR模型表现出不规则的主动脉内膜和无序的平滑肌细胞。MHR模型中有78个差异表达基因,和七个枢纽基因,包括USP18,被确认。在体外用Ang处理的HUVEC中,USP18过表达促进增殖并减少凋亡和氧化应激。此外,JAK/STAT通路被确定为USP18下游信号通路,USP18过表达抑制JAK/STAT通路相关蛋白的表达。最后,USP18通过促进细胞增殖抑制MHR进展,逆转细胞凋亡和氧化应激,并抑制JAK/STAT通路。
Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (
USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover,
USP18 downstream signaling pathways in MHR were screened, and the effects of
USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including
USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a
USP18 downstream signaling pathway, and
USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively,
USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.