Qin Ying, Dong Tao, Jiang Wan, Ding Wen, Zhan Tao, Du Juan, Zhao Ren, Shen Bing, Chen Jiexia
School of Basic Medicine Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.
Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
EXCLI J. 2020 Nov 6;19:1496-1511. doi: 10.17179/excli2020-2740. eCollection 2020.
High-salt diets may increase both hypertension and risk of cardiovascular diseases. Although high-salt diets can result in hypertension and impaired vascular function, the molecular mechanisms underlying these dysfunctions are not fully known. Thus, the aims of the present study were to identify key proteins and their signaling pathways and associated molecular mechanisms that may contribute to, as well as be potential biomarkers of, the pathogenesis of hypertension-related cardiovascular diseases. To that end, the present study identified and quantitated serum proteins that were differentially expressed in male rats fed regular chow (n = 4) and those fed a high-salt diet (n = 4) to induce hypertension. The serum was collected from both groups, and the proteins differentially expressed in the serum were identified and quantitated using isobaric tags for relative and absolute quantitation combined with liquid chromatography-tandem mass spectrometry. Of 396 identified proteins, 24 were differentially expressed between the groups: 19 proteins were significantly ( < 0.05) upregulated (> 1.2 fold change), and 5 were significantly downregulated (< 0.8 fold change). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these differentially expressed proteins may contribute to cardiovascular diseases via the roles they play in endothelial function, vascular remodeling, the coagulation cascade, and the complement system. In addition, phagosome processes and the integrin-associated focal adhesion signaling pathway were determined to be potential underlying molecular mechanisms. The key proteins identified in this study warrant further development as new therapeutic targets or biomarkers of cardiovascular diseases associated with high-salt diet-induced hypertension.
高盐饮食可能会增加高血压和心血管疾病的风险。尽管高盐饮食会导致高血压和血管功能受损,但其功能障碍背后的分子机制尚未完全明确。因此,本研究的目的是确定关键蛋白质及其信号通路以及相关分子机制,这些机制可能导致高血压相关心血管疾病的发病,并成为其潜在的生物标志物。为此,本研究对喂食普通饲料的雄性大鼠(n = 4)和喂食高盐饮食以诱发高血压的雄性大鼠(n = 4)血清中差异表达的蛋白质进行了鉴定和定量。收集两组大鼠的血清,采用相对和绝对定量的等压标签结合液相色谱 - 串联质谱法对血清中差异表达的蛋白质进行鉴定和定量。在鉴定出的396种蛋白质中,两组之间有24种差异表达:19种蛋白质显著上调(<0.05)(变化倍数>1.2),5种蛋白质显著下调(<0.8倍变化)。基因本体论和京都基因与基因组百科全书富集分析表明,这些差异表达的蛋白质可能通过在内皮功能、血管重塑、凝血级联反应和补体系统中的作用导致心血管疾病。此外,吞噬体过程和整合素相关粘着斑信号通路被确定为潜在的分子机制。本研究中鉴定出的关键蛋白质值得进一步开发,作为与高盐饮食诱导的高血压相关的心血管疾病的新治疗靶点或生物标志物。