title: Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages.
abstract: 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 rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males.
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Vijay
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Moland
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Kwekel
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Fuscoe
authors.affiliation: Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors.forename: Varsha G
authors.initials: VG
authors.lastname: Desai
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D004734:Energy Metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054629:Genome, Mitochondrial; D006321:Heart / Q000254:growth & development*; D008297:Male; D008929:Mitochondria, Heart / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
chemical_list: D024101:Mitochondrial Proteins