iTRAQ-based proteomics reveals serum protein changes in hypertensive rats induced by a high-salt diet

Abstract

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 (P < 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.