title: Estrogenic modulation of inflammation-related genes in male rats following volume overload.
abstract: Our laboratory has previously reported significant increases of the proinflammatory cytokine TNF-α in male hearts secondary to sustained volume overload. These elevated levels of TNF-α are accompanied by left ventricular (LV) dilatation and cardiac dysfunction. In contrast, estrogen has been shown to protect against this adverse cardiac remodeling in both female and male rats. The purpose of this study was to determine whether estrogen has an effect on inflammation-related genes that contribute to this estrogen-mediated cardioprotection. Myocardial volume overload was induced by aortocaval fistula in 8 wk old male Sprague-Dawley rats (n = 30), and genes of interest were identified using an inflammatory PCR array in Sham, Fistula, and Fistula + Estrogen-treated (0.02 mg/kg per day beginning 2 wk prior to fistula) groups. A total of 55 inflammatory genes were modified (≥2-fold change) at 3 days postfistula. The number of inflammatory gene was reduced to 21 genes by estrogen treatment, whereas 13 genes were comparably modulated in both fistula groups. The most notable were TNF-α, which was downregulated by estrogen, and the TNF-α receptors, which were differentially regulated by estrogen. Specific genes related to arachidonic acid metabolism were downregulated by estrogen, including cyclooxygenase-1 and -2. Finally, gene expression for the β1-integrin cell adhesion subunit was significantly upregulated in the LV of estrogen-treated animals. Protein levels reflected the changes observed at the gene level. These data suggest that estrogen provides its cardioprotective effects, at least in part, via genomic modulation of numerous inflammation-related genes.
authors.affiliation: Cell Biology and Anatomy, University of South Carolina-School of Medicine, Columbia, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McLarty
authors.forename: Giselle C
authors.initials: GC
authors.lastname: Meléndez
authors.forename: Scott P
authors.initials: SP
authors.lastname: Levick
authors.forename: Shanté
authors.initials: S
authors.lastname: Bennett
authors.forename: Tara
authors.initials: T
authors.lastname: Sabo-Attwood
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Brower
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Janicki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D015153:Blotting, Western; D002306:Cardiac Volume / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005402:Fistula / Q000601:surgery; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D004967:Estrogens; D019012:Integrin beta1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha