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Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages
Vikrant Vijay1, Tao Han1, Carrie L Moland1
1Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, United States of America.
Insights
Mitochondria gene expression differs between male and female rat hearts across ages, revealing sex-based variations in cardiac energy metabolism that may influence cardiovascular disease susceptibility.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Biology
- Genomics
Background:
- Cardiovascular disease (CVD) is a leading global cause of death, with sex and age as significant risk factors.
- Mitochondria are crucial for heart function, and their structure/function regulation may affect CVD susceptibility.
- Understanding sex-related differences in mitochondrial function is key to identifying CVD risk factors.
Purpose of the Study:
- To investigate the role of mitochondria in sex-related differences in cardiovascular disease (CVD) susceptibility.
- To analyze basal expression levels of mitochondria-related genes in male and female rat hearts across different age groups.
Main Methods:
- Whole genome expression profiling of heart tissue from young, adult, and old male and female Fischer 344 rats.
- Analysis of 670 unique genes related to various mitochondrial functions.
- Gene Ontology analysis to identify sex-influenced biological pathways.
Main Results:
- Significant sexual dimorphism in gene expression was observed across all age groups (46 genes in young, 114 in adult, 41 in old rats).
- Sex influenced cardiac energy metabolism pathways, with differences in fatty acid metabolism gene expression in young and adult rats.
- Oxidative phosphorylation genes showed sex-specific expression patterns, with higher female expression in old rats, and lower apoptotic gene expression in females across all ages.
Conclusions:
- Basal differences in cardiac mitochondrial gene expression between sexes suggest a role in CVD susceptibility.
- Sex-based variations in cardiac energy metabolism and apoptosis regulation may contribute to differential CVD risk and cardiac preservation.
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.
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