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The article presents a study on the molecular mechanisms that underlies the inhibitory effects of estrogen replacement regarding pressure over-load-induced left ventricular (LV) hypertrophy in the mouse transverse aortic constriction (TAC) model. It provides further laboratory investigation on the influences of hypertrophy and calcineurin signaling. A demonstration of cellular ribonucleic acid (RNA) isolation from myocardial samples is also depicted.

The effects of estrogen on vascular function have been studied extensively; however, much less is known regarding the effect of estrogen on myocardial function and cardiomyocyte biology. We recently examined the effects of estrogen on infarct size and left ventricular remodeling after induction of myocardial infarction by permanent coronary ligation in ovariectomized female mice. These studies demonstrated that physiologic replacement with 17β-estradiol (E2) reduced infarct size and reduced cardiomyocyte apoptosis at 24 and 72 hours post–myocardial infarction. In vivo, physiologic E2 replacement rapidly activated the Akt signaling pathway within the myocardium. In vitro, physiologic concentrations of E2 rapidly activated Akt via estrogen receptor α (ERα) and phosphoinositide-3 (PI3)-kinase-dependent mechanisms. Moreover, estrogen mitigated anthracycline-induced apoptosis in vitro via ER- and PI3-kinase-Akt-dependent mechanisms. Our data therefore support that estrogen favorably influences cardiomyocyte survival both in a coronary occlusion model in vivo and in cultured cardiomyocytes in vitro. Further work is necessary to more completely understand the complex effects of sex hormones on cardiomyocyte biology. [Copyright &y& Elsevier]

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT1aR subtype in post-MI remodeling and whether gentler differences exist in the patterns of remodeling in wild-type and AT1aR knockout (KO) mice. AT1aR-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT1aR-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT1aR-KO mice compared with wild-type mice. Male and female wild-type and male AT1aR-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT1aR-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT1aR-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT1aR gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT1aR. Further work is necessary to explore the potential mechanisms underlying these gender-based differences. [ABSTRACT FROM AUTHOR]

Cardiomyocyte hypertrophy and extracellular matrix remodeling, primarily mediated by inflammatory cytokine-stimulated cardiac fibroblasts, are critical cellular events in cardiac pathology. The molecular components governing these processes remain nebulous, and few genes have been linked to both hypertrophy and matrix remodeling. Here we show that p8, a small stress-inducible basic helix-loop-helix protein, is required for endothelin- and α-adrenergic agonist-induced cardiomyocyte hypertrophy and for tumor necrosis factor-stimulated induction, in cardiac fibroblasts, of matrix metalloproteases (MMPs) 9 and 13--MMPs linked to general inflammation and to adverse ventricular remodeling in heart failure. In a stimulus-dependent manner, p8 associates with chromatin containing c-Jun and with the cardiomyocyte atrial natriuretic factor (anf) promoter and the cardiac fibroblast mmp9 and mmp13 promoters, established activator protein 1 effectors. p8 is also induced strongly in the failing human heart by a process reversed upon therapeutic intervention. Our results identify an unexpectedly broad involvement for p8 in key cellular events linked to cardiomyocyte hypertrophy and cardiac fibroblast MMP production, both of which occur in heart failure. [ABSTRACT FROM AUTHOR]