Key result
Extensive myocardial infarction significantly decreased NHE1 mRNA and protein expression by 21.5% and 22.0%, respectively, in the non-infarcted myocardium of rats 24 hours after coronary ligation.
Effect estimate: 21.5% decrease in mRNA and 22.0% decrease in protein
p-value: p=<0.05
Extensive myocardial infarction leads to a spontaneous decrease in NHE1 mRNA and protein expression in non-infarcted myocardium, which may represent a compensatory cardioprotective mechanism against cell injury.
Suggests compensatory cardioprotection post-MI; leaves open NHE1 targeting in human trials.
Although cardiac NHE1 is activated during myocardial ischemia and reperfusion injury, little is known about changes in expression in non-infarcted myocardium after acute myocardial infarction (AMI). The purpose of this study was to examine left ventricular function and region dependent NHE1 expression after myocardial infarction. Therefore, we produced two AMI models in rats, a small infarction model which was continuously ligated at the branches of the left coronary artery, and an extensive infarction model continuously ligated at the root of the artery. We examined NHE1 mRNA expression using RNase protection assay and protein levels using Western blot analysis in non-infarcted myocardium during the 24 hour period after AMI. The level of NHE1 mRNA and protein expression in the whole heart including the infarcted myocardium did not change after a small infarction. On the other hand, in the case of an extensive infarction, the levels of NHE1 mRNA and protein expression decreased significantly by 21.5% (P<0.05) and by 22.0% (P<0.05), respectively, in non-infarcted myocardium. Left ventricular systolic pressure (LVSP) decreased significantly by 13% and 38% with the branch and root ligation, respectively. However, left ventricular end-diastolic pressure (LVEDP) only increased with the root ligation. These results indicate that NHE1 expression decreased in response to extensive myocardial infarction only in non-infarcted myocardium. The present study may be important in furthering the understanding of NHE1 in myocardial infarction and suggests that decreased expression of NHE1 in non-infarcted myocardium may decrease the extent of cardiac cell injury.
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Shimohama et al. (2002) studied Acute Myocardial Infarction (n=71). Extensive myocardial infarction (root ligation) vs. Small myocardial infarction (branch ligation) and sham operation was evaluated on NHE1 mRNA and protein expression in non-infarcted myocardium (21.5% decrease in mRNA and 22.0% decrease in protein, p=<0.05). Extensive myocardial infarction significantly decreased NHE1 mRNA and protein expression by 21.5% and 22.0%, respectively, in the non-infarcted myocardium of rats 24 hours after coronary ligation.
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