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Gene expression profiling of age-related changes in coronary arterioles following intravenous stromal vascular fraction using RNA-seq

ABSTRACT: The goal of this study is to examine age-related changes in the beta-1 adrenergic receptor dependent vasodilaiton in coronary microvessels from young, old, and old rats treated intravenously with stromal cells isolated from adipose tissue (SVF). We have shown that an aged coronary microvasculature has impaired vasodilation to adrenergic agonists and that a single treatment of SVF cells ameliorates the impaired vasodilation but the therapeutic mechanism is unknown.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE184674 | GEO | 2022/09/15

REPOSITORIES: GEO

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Project description:Functional decline and structural alterations of the brain microvasculature are associated with cognitive impairment and development of dementias such as Alzheimer’s disease during aging. Although mechanisms of leading to microvascular changes during aging are not clear, the loss of mitochondria and reduced efficiency of remaining mitochondria appear to play a major role. While pharmacological agents which target mitochondria such as SS-31 have been shown to be effective in beneficial during aging and diseases, the full extent on mitochondrial- and non-mitochondrial proteins in the brain microvasculature has not been examined. We tested the hypothesis that attenuation of aging-associated changes in the brain microvascular proteome via targeting mitochondria represents a therapeutic option in the aging brain. We used male, aged (>18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31 or vehicle saline. Baseline cerebral blood flow (CBF) was determined using laser speckle imaging during the two-week treatment period. Then, isolated cortical microvessels (MVs), composed of end arterioles, capillaries, and venules, were used for Orbitrap Eclipse Tribrid mass spectrometry. Baseline CBF was similar between the groups, whereas bioinformatic analysis revealed substantial differences in protein abundance of cortical MVs between SS-31 and vehicle groups. Specifically, we identified 6,266 proteins in our data set from which 12% were mitochondrial or mitochondria associated. 107 of these proteins were significantly differentially expressed between the treatment and vehicle groups, and were associated with the oxidative phosphorylation, metabolism, antioxidant defense system, or mitochondrial dynamics. Administration of SS-31 also affected many non-mitochondrial proteins. Our findings suggest that mitochondria in the microvasculature represent a therapeutic target in the aging brain, and widespread changes in the proteome may underlie the mechanisms of rejuvenating actions of SS-31 in the aging phenotype.

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Gene expression profiling of age-related changes in coronary arterioles following intravenous stromal vascular fraction using RNA-seq

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