Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice

Maria Belen Rabaglino, Masaki Wakabayashi, James Todd Pearson, Lars Jørn Jensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Aging is associated with hypertension and brain blood flow dysregulation, which are major risk factors for cardiovascular and neurodegenerative diseases. Structural remodeling, endothelial dysfunction, or hypercontractility of resistance vessels may cause increased total peripheral resistance and hypertension. Recent studies showed that G protein- and RhoA/Rho-kinase pathways are involved in increased mean arterial pressure (MAP) and arterial tone in middle-aged mice. We aimed to characterize the age-dependent changes in the vascular proteome in normal laboratory mice using mass spectrometry and bioinformatics analyses on middle cerebral arteries and mesenteric resistance arteries from young (3 months) vs. middle-aged (14 months) mice. In total, 31 proteins were significantly affected by age whereas 172 proteins were differentially expressed by vessel type. Hierarchical clustering revealed that 207 proteins were significantly changed or clustered by age. Vitamin B6 pathway, Biosynthesis of antibiotics, Regulation of actin cytoskeleton and Endocytosis were the top enriched KEGG pathways by age. Several proteins in the RhoA/Rho-kinase pathway changed in a manner consistent with hypertension and dysregulation of cerebral perfusion. Although aging had a less profound effect than vessel type on the resistance artery proteome, regulation of actin cytoskeleton, including the RhoA/Rho-kinase pathway, is an important target for age-dependent hypertension.
Original languageEnglish
Article number111594
JournalMechanisms of Ageing and Development
Volume200
Number of pages17
ISSN0047-6374
DOIs
Publication statusPublished - 2021

Keywords

  • Aging
  • Hypertension
  • Cerebral arteries
  • Resistance arteries
  • Proteomics
  • Bioinformatics

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