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Temporal Proteomic Remodeling of Cerebral Arteries in Hypertensive Rats Reveals Progressive Vascular Changes Linked to Brain Diseases

ABSTRACT: Hypertension is a significant risk factor for several brain diseases, including stroke and dementia, yet the molecular mechanisms conferring to these risks remain poorly understood. In this study, we investigated temporal proteomic remodeling of the cerebrovasculature in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls at 30 and 40 weeks of age, representing the effect of untreated hypertension from early adulthood to midlife. Using discovery-based proteomics, RNA-sequencing data and comparison to previously published data, we have demonstrated a significant age-dependent change in the protein composition of the cerebrovasculature in the SHR model, which is partly mediated via the serum response factor (SRF) regulon. We identified a transient upregulation of mitotic (M-phase) proteins at 30 weeks, indicative of maladaptive smooth muscle proliferation. By 40 weeks, the expression of these proteins was normalized; however, extracellular matrix (ECM)-associated proteins diverged substantially. The ECM remodeling was supported by increased media-to-lumen ratio and collagen deposition from histological analysis. Our findings reveal a novel temporal window during which hypertension drives a progressive remodeling of the cerebrovasculature. Collectively, the data supports a critical intervention window in early to midlife hypertension to prevent a molecular profile with brain disease-linked features.

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ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cerebral Artery

SUBMITTER: Joakim Bastrup

LAB HEAD: Thomas A. Jepps

PROVIDER: PXD065658 | Pride | 2025-11-17

REPOSITORIES: Pride

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Temporal Proteomic Remodeling of Cerebral Arteries in Hypertensive Rats Reveals Progressive Vascular Changes Linked to Brain Diseases

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