Decreased Expression of Na+/H+ Exchanger Isoform 1 (NHE1) in Non-infarcted Myocardium after Acute Myocardial Infarction.

Abstract

SUMMARYAlthough 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 noninfarcted 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. (Jpn Heart J 2002; 43: 273-282)

HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange

“…While the NHE1 mRNA level was strongly upregulated only after acidic SI, this pH dependence was not detected at the protein level, a phenomenon that we currently cannot explain. Similar to our findings, NHE1 mRNA and protein levels were reduced in the noninfarcted part of rat myocardium after myocardial infarction (52), and NHE1 upregulation during reperfusion after I/R was also reported in rat hearts (9,13). In accordance with the lack of detectable caspase-3 activation during SI per se, Western blot analysis did not reveal the presence of NHE1 cleavage products (data not shown); hence, it seems likely that the downregulation of NHE1 protein levels in SI reflects the reduction at the mRNA level.…”

Age, cell signalling and cardioprotection

“…Another explanation for the negative results of the clinical trials is that the level of NHE may have varied considerably among the participants. Sodium-hydrogen exchanger 1 mRNA has been reported to increase after an ischaemic episode except when the myocardium has been exposed to ischaemic preconditioning (Dyck et al 1995, decreased expression of NHE1 has been observed following myocardial infarction (Shimohama et al 2002), and increased activity with no change in expression has been found in patients with chronic endstage heart failure . In the clinical trials, the subjects were administered treatments following initial symptoms of cardiovascular failure that may have altered the NHE in various ways thereby attenuating the effect of an NHE inhibitor.…”

Na+/H+exchange inhibitor cariporide attenuates skeletal muscle infarction when administered before ischemia or reperfusion

“…The methods were similar to those previously reported for cardiac muscle of laboratory animals (8,49). Frozen muscle biopsies (ϳ200 mg) were cut into small pieces and homogenized for 30 s in 2 ml of ice cold lysis buffer containing 50 mM Tris ⅐ HCl (pH 7.4), 50 mM EDTA, 150 mM NaCl, 0.1% Triton 100, 1 mg/ml pepstatin, 200 mM phenylmethyl sulfonyl fluoride, and 1 mg/ml leupeptin.…”