TY - JOUR

T1 - Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice

AU - Rabaglino, Maria B.

AU - Wakabayashi, Masaki

AU - Pearson, James Todd

AU - Jensen, Lars Jørn

PY - 2021

Y1 - 2021

N2 - 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 on the resistance artery proteome than on vessel type, regulation of actin cytoskeleton, including the RhoA/Rho-kinase pathway, is an important target for age-dependent hypertension.

AB - 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 on the resistance artery proteome than on vessel type, regulation of actin cytoskeleton, including the RhoA/Rho-kinase pathway, is an important target for age-dependent hypertension.

KW - Faculty of Health and Medical Sciences

KW - Aging

KW - Hypertension

KW - Cerebral Arteries

KW - resistance arteries

KW - proteomics

KW - bioinformatics

U2 - 10.1016/j.mad.2021.111594

DO - 10.1016/j.mad.2021.111594

M3 - Journal article

C2 - 34756926

VL - 200

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

M1 - 111594

ER -