Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Rat Life Cycle (RLC) Heart Gene Expression Data

ABSTRACT: Cardiovascular disease (CVD) is the leading cause of mortality, with sex and age being strong risk factors. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. We analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female untreated control rats at different ages to identify potential role of mitochondria in differential susceptibility to CVD between the sexes. Hearts from 5 male and 5 female rats at three different ages (young (8-week), adult (21-week), and old (78-week)) were used for investigation of sex-related differences in expression levels of genes. At each age, rats were humanely euthanized by CO2 asphyxiation and whole hearts were removed quickly, flash frozen in liquid nitrogen, and stored at -80ËC until further investigation. The frozen hearts were individually ground into powder in liquid nitrogen using a mortar and pestle chilled on dry ice. Total RNAs were extracted from heart tissue powder and gene expression was measured using Agilent Rat Whole Genome Microarrays (4 x 44k format; Agilent Technologies, Inc.).

ORGANISM(S): Rattus norvegicus

SUBMITTER: Vikrant Vijay

PROVIDER: E-GEOD-58204 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages.

Vijay Vikrant V Han Tao T Moland Carrie L CL Kwekel Joshua C JC Fuscoe James C JC Desai Varsha G VG

PloS one 20150123 1

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female ra ...[more]

PMID: 25615628

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Project description:The beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics. Experiment Overall Design: RNA was isolated from hearts obtained from non-transgenic mice, AC5 transgenic mice, beta1-Gly389 transgenic mice and beta1-Arg389 transgenic mice at 90 days of age. 6 biological replicates were used for each genotype.

Dataset Information

Rat Life Cycle (RLC) Heart Gene Expression Data

Publications

Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages.

Similar Datasets

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