{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:39:32Z","timestamp":1788255572462,"version":"build-2803163510"},"reference-count":58,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2010,8]]},"abstract":"\n In myocardial disease, elevated expression and activity of Na\n +<\/jats:sup>\n \/H\n +<\/jats:sup>\n exchanger isoform 1 (NHE1) are detrimental. To better understand the involvement of NHE1, transgenic mice with elevated heart-specific NHE1 expression were studied. N-line mice expressed wild-type NHE1, and K-line mice expressed activated NHE1. Cardiac morphology, interstitial fibrosis, and cardiac function were examined by histological staining and echocardiography. Differences in gene expression between the N-line or K-line and nontransgenic littermates were probed with genechip analysis. We found that NHE1 K-line (but not N-line) hearts developed hypertrophy, including elevated heart weight-to-body weight ratio and increased cross-sectional area of the cardiomyocytes, interstitial fibrosis, as well as depressed cardiac function. N-line hearts had modest changes in gene expression (50 upregulations and 99 downregulations, P < 0.05), whereas K-line hearts had a very strong transcriptional response (640 upregulations and 677 downregulations, P < 0.05). In addition, the magnitude of expression alterations was much higher in K-line than N-line mice. The most significant changes in gene expression were involved in cardiac hypertrophy, cardiac necrosis\/cell death, and cardiac infarction. Secreted phosphoprotein 1 and its signaling pathways were upregulated while peroxisome proliferator-activated receptor \u03b3 signaling was downregulated in K-line mice. Our study shows that expression of activated NHE1 elicits specific pathways of gene activation in the myocardium that lead to cardiac hypertrophy, cell death, and infarction.\n <\/jats:p>","DOI":"10.1152\/physiolgenomics.00064.2010","type":"journal-article","created":{"date-parts":[[2010,5,11]],"date-time":"2010-05-11T22:34:48Z","timestamp":1273617288000},"page":"374-383","source":"Crossref","is-referenced-by-count":44,"title":["Elevated myocardial Na\n +<\/sup>\n \/H\n +<\/sup>\n exchanger isoform 1 activity elicits gene expression that leads to cardiac hypertrophy"],"prefix":"10.1152","volume":"42","author":[{"given":"Jin","family":"Xue","sequence":"first","affiliation":[{"name":"Departments of 1Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Mraiche","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pediatrics, University of Alberta, Edmonton, Alberta 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