Identification of novel proteins and mechanistic pathways associated with early-onset hypertension by deep proteomic mapping of resistance arteries

Abstract

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Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension

“…The mass spectrometer was operated in DIA PASEF mode with 1.1 s cycle time and TIMS ramp time of 100.0 ms. MS scan range was set to 100-1700 m/z. MS raw files from a previous publication 7 were download from the ProteomeXchange Consortium via PRIDE with the identifier PXD026051. The files contained DIA-MS information about mesenteric and renal arteries from 12-week-old SHR and WKY.…”

“…Statistical comparisons between 12-week old rat groups was made using the limma package for R 17,18 to enable batch correction and calculation of statistical significance levels and fold change difference per protein. Furthermore, two-sided Student's t-test in Perseus was used to compare PFC groups, pre-hypertensive groups as well as previously published mesenteric and renal artery data 7 , with permutation-based FDR (<0.05) and 250 randomizations. Missing values were only imputed for PCA (width =0.4, down shift = 1.8).…”

“…Hierarchical clustering was created based on z-scored LFQ values and generated by average linkage, preprocessing with k-means, and Euclidean distance. The z-score normalization was calculated by subtracting mean intensity from each protein value across all samples followed by division by the standard deviation 7 . ClueGO (v2.5.8) 23 in Cytoscape (v3.9.1) 24 was used to generate protein-protein interaction networks and enrichment analysis of significantly regulated proteins.…”

“…ClueGO (v2.5.8) 23 in Cytoscape (v3.9.1) 24 was used to generate protein-protein interaction networks and enrichment analysis of significantly regulated proteins. The enrichment analysis was performed as previously described 7 ; Rattus norvegicus was selected as organism, and the Gene Ontology (GO) biological processes (GO-BiologicalProcess, CellularComponent,…”

“…In hypertension, a general narrowing of the large resistance arteries through to the precapillary microcirculation is associated with eutrophic and hypertrophic remodeling of the arterial wall in most vascular beds [3][4][5] . We, and others, have demonstrated that arterial remodeling occurs in certain systemic arteries soon after the onset of hypertension (12-weeks old) in the spontaneously hypertensive rat (SHR) 6 , a model that is considered to resemble the main features of essential hypertension in humans without confounding lifestyle and environmental factors 7 . Although the remodeling processes are a key feature of hypertension, the mechanistic pathways involved are not understood fully.…”