Immediate response of myocardium to pressure overload includes transient regulation of genes associated with mitochondrial bioenergetics and calcium availability

Abstract

Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca+2 ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability.

G 13 -Mediated Signaling Pathway Is Required for Pressure Overload–Induced Cardiac Remodeling and Heart Failure

“…This discrepancy might be explained by incomplete inhibition of G␣ 13 -mediated signaling in p115-RGS transgenic mice, for example, resulting from the fact that the ␣MHC promoter driving expression of the inhibitory peptide is downregulated as early as 6 hours after the onset of pressure overload. 34 In addition, the ␣MHC promoter is active already during embryogenesis, potentially causing developmental defects and/or complex compensatory responses. In our model of tamoxifen-inducible Cre-mediated .…”

Pressure-overload-induced angiotensin-mediated early remodeling in mouse heart

“…Consistent with these studies, we observed that 1 week was sufficient to induce hypertrophy using similarly sized needles for ligation. A separate report [ 27 ] documented changes in LV weight to body weight ratio from one hour to 48 hours post-operation. In the initial 48 hours, no significant change was detected, consistent with our findings.…”