13 research outputs found
Sex-based differences in myocardial gene expression in recently deceased organ donors with no prior cardiovascular disease
<div><p>Sex differences in the development of the normal heart and the prevalence of cardiomyopathies have been reported. The molecular basis of these differences remains unclear. Sex differences in the human heart might be related to patterns of gene expression. Recent studies have shown that sex specific differences in gene expression in tissues including the brain, kidney, skeletal muscle, and liver. Similar data is limited for the heart. Herein we address this issue by analyzing donor and post-mortem adult human heart samples originating from 46 control individuals to study whole-genome gene expression in the human left ventricle. Using data from the genotype tissue expression (GTEx) project, we compared the transcriptome expression profiles of male and female hearts. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. The majority of differentially expressed autosomal genes were those involved in the regulation of inflammation, which has been found to be an important contributor to left ventricular remodeling. Specifically, genes on autosomal chromosomes encoding chemokines with inflammatory functions (e.g. CCL4, CX3CL1, TNFAIP3) and a gene that regulates adhesion of immune cells to the endothelium (e.g., VCAM1) were identified with sex-specific expression levels. This study underlines the relevance of sex as an important modifier of cardiac gene expression. These results have important implications in the understanding of the differences in the physiology of the male and female heart transcriptome and how they may lead to different sex specific difference in human cardiac health and its control.</p></div
Five top canonical pathways for female and male biased genes.
<p>Five top canonical pathways for female and male biased genes.</p
Female up-regulated genes in inflammatory and heart development pathways.
<p>Female up-regulated genes in inflammatory and heart development pathways.</p
Differentially expressed genes heat map.
<p>Heat map showing differentially expressed genes between male and female LV tissues.</p
Top biological functions, molecular functions and cellular components of female biased genes.
<p>Top biological functions, molecular functions and cellular components of female biased genes.</p
Demographic and clinical variables of cohort.
<p>Demographic and clinical variables of cohort.</p
5 top MGI mammalian phenotype for female biased genes.
<p>5 top MGI mammalian phenotype for female biased genes.</p
Chromosomal enrichment.
<p>For each chromosome, the number of male- and female-biased genes was computed, the table below the graph lists chromosomes that passed the test for enrichment by Fisher exact test with Benjamini correction, P < 0.05.</p
Female heart over expressed genes involve in inflammatory pathways.
<p>The bar graphs show the read count and error bars represent standard deviation.</p
Age and sex stratified comparisons of differentially expressed genes, q value <0.05 and fold change > 1.5.
<p>Age and sex stratified comparisons of differentially expressed genes, q value <0.05 and fold change > 1.5.</p