TY - JOUR
T1 - Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice
AU - Rabaglino, Maria Belen
AU - Wakabayashi, Masaki
AU - Pearson, James Todd
AU - Jensen, Lars Jørn
N1 - Funding Information:
Japan Society for the Promotion of Science (JSPS) and the JSPS Alumni Club of Denmark are gratefully acknowledged for providing a Bridge fellowship to LJJ, which made this collaboration possible. Furthermore, we thank the National Cerebral and Cardiovascular Center Research Institute (Osaka, Japan) for hosting LJJ during a Bridge Fellowship visit in the early spring of 2020.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/12
Y1 - 2021/12
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 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.
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 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.
KW - Aging
KW - Bioinformatics
KW - Cerebral arteries
KW - Hypertension
KW - Proteomics
KW - Resistance arteries
UR - http://www.scopus.com/inward/record.url?scp=85118883047&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2021.111594
DO - 10.1016/j.mad.2021.111594
M3 - Article
C2 - 34756926
AN - SCOPUS:85118883047
SN - 0047-6374
VL - 200
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
M1 - 111594
ER -