Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice. (December 2021)

• Record Type: Journal Article
• Authors: Rabaglino, Maria Belen; Wakabayashi, Masaki; Pearson, James Todd; Jensen, Lars Jørn
• Is Part Of: Mechanisms of ageing and development. Volume 200(2021)
• Publication Date: 2021-12
• Subjects: DTT dithiothreitol -- IAA iodoacetamide -- LC–MS/MS liquid chromatography-coupled tandem mass spectrometry -- Lys-C lysyl endopeptidase -- MAP mean arterial pressure -- MCA middle cerebral artery -- MRA mesenteric resistance artery -- NO nitric oxide -- SDC sodium deoxycholate -- SLS sodium lauroyl sarcosinate -- TFA trifluoroacetic acid -- TPR total peripheral resistance -- VSMC vascular smooth muscle cell; Aging -- Hypertension -- Cerebral arteries -- Resistance arteries -- Proteomics -- Bioinformatics; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2021.111594
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: 31 proteins were differentially expressed by age whereas 172 proteins were differentially expressed by vessel type in young vs. middle-aged mice. Vitamin B6 pathway, Biosynthesis of antibiotics, Regulation of actin cytoskeleton and Endocytosis were the top enriched KEGG pathways by age. Proteins in the RhoA/Rho-kinase pathway changed in a manner consistent with hypertension and dysregulation of cerebral perfusion. Regulation of actin cytoskeleton including the RhoA/Rho-kinase pathway is an important new target to treat age-dependent hypertension. 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.