Abstract
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.
Highlights
Hypertension is the main risk factor for cardiovascular diseases and is a major global health burden, with increasing prevalence[1]
blood pressure (BP) in the spontaneously hypertensive rat (SHR) begins to increase at ~6-weeks of age, Journal Pre-proof leading to a chronic elevated BP from ~12-weeks[14]
Our study was designed to capture the critical changes that occur in the arterial wall during the early-onset of high BP, these time points were selected to represent pre-hypertensive and early-onset hypertensive phenotypes and avoid confounding pathological changes associated with long-term, chronic hypertension
Summary
Hypertension is the main risk factor for cardiovascular diseases and is a major global health burden, with increasing prevalence[1]. Many studies have investigated specific genes, proteins and pathways that are altered in arteries from hypertensive animals and humans, there is no overview of the changes that occur in arteries during hypertension. Resistance arteries undergo eutrophic and/or hypertrophic remodeling, which contributes to increased peripheral resistance[3]. In patients with essential hypertension and the spontaneously hypertensive rat (SHR), inward eutrophic remodeling predominates[3]. Several contractile and dilatory mechanisms are compromised in arteries from hypertensive animals and humans, which contribute to the development and persistence of hypertension. These maladaptive changes in the vessel wall influence the development and cardiovascular complications of hypertension. Proteins have been implicated in vascular remodeling in hypertension, these proteins do not work in isolation
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