Identification of novel proteins and mechanistic pathways associated with early-onset hypertension by deep proteomic mapping of resistance arteries
| Autor: | Joakim A. Bastrup, Christian Aalkjær, Thomas A. Jepps |
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| Rok vydání: | 2022 |
| Předmět: |
BP
blood pressure Proteomics hypertension extracellular matrix KEGG Kyoto Encyclopedia of Genes and Genomes Rats Inbred WKY Biochemistry VSMC vascular smooth muscle cell Mass Spectrometry arteries ROS reactive oxygen species vascular Rats Inbred SHR GO Gene Ontology Animals DIA-MS data-independent acquisition–mass spectrometry Molecular Biology remodeling PCA principal component analysis Cell Biology ECM extracellular matrix Mesenteric Arteries Rats MS mass spectrometry WKY Wistar Kyoto Vascular Resistance SHR spontaneously hypertensive rat Research Article |
| Zdroj: | The Journal of Biological Chemistry Bastrup, J A, Aalkjær, C & Jepps, T A 2022, ' Identification of novel proteins and mechanistic pathways associated with early-onset hypertension by deep proteomic mapping of resistance arteries ', Journal of Biological Chemistry, vol. 298, no. 1, 101512 . https://doi.org/10.1016/j.jbc.2021.101512 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.101512 |
| Popis: | Resistance arteries are small blood vessels that create resistance to blood flow. In hypertension, resistance arteries undergo remodeling, affecting their ability to contract and relax appropriately. To date, no study has mapped the hypertension-related proteomic changes in resistance arteries. Using a novel data-independent acquisition-mass spectrometry (DIA-MS) approach, we determined the proteomic changes in small mesenteric and renal arteries in pre- and early-onset hypertension from the spontaneously hypertensive rat (SHR) model, which represents human primary hypertension. Compared with normotensive controls, mesenteric arteries from 12-week-old SHRs had 286 proteins that were significantly up- or downregulated, whereas 52 proteins were identified as up- or downregulated in mesenteric arteries from 6-week-old SHRs. Of these proteins, 18 were also similarly regulated in SHR renal arteries. Our pathway analyses reveal several novel pathways in the pathogenesis of hypertension. Finally, using a matrisome database, we identified 38 altered extracellular-matrix-associated proteins, many of which have never previously been associated with hypertension. Taken together, this study reveals novel proteins and mechanisms that are associated with early-onset hypertension, thereby providing novel insights into disease progression. |
| Databáze: | OpenAIRE |
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