{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:52:42Z","timestamp":1772794362814,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T00:00:00Z","timestamp":1435622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>What is the potential role of endothelial NO production via overexpression of the <jats:sc>l<\/jats:sc>\u2010arginine transporter, CAT1, as a mitigator of cardiac hypertrophy?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Augmentation of endothelium\u2010specific <jats:sc>l<\/jats:sc>\u2010arginine transport via CAT1 can attenuate pressure\u2010overload\u2010dependent cardiac hypertrophy and fibrosis. Our findings support the conclusion that interventions that improve endothelial <jats:sc>l<\/jats:sc>\u2010arginine transport may provide therapeutic utility in the setting of myocardial hypertrophy. Such modifications may be introduced by exercise training or locally delivered gene therapy, but further experimental and clinical studies are required.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Endothelial dysfunction has been postulated to play a central role in the development of cardiac hypertrophy, probably as a result of reduced NO bioavailability. We tested the hypothesis that increased endothelial NO production, mediated by increased <jats:sc>l<\/jats:sc>\u2010arginine transport, could attenuate pressure\u2010overload\u2010induced cardiac hypertrophy. Echocardiography and blood pressure measurements were performed 15\u00a0weeks after transverse aortic constriction (TAC) in wild\u2010type (WT) mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) and in mice with endothelium\u2010specific overexpression of the <jats:sc>l<\/jats:sc>\u2010arginine transporter, CAT1 (CAT+; <jats:italic>n<\/jats:italic>\u00a0=\u00a012). Transverse aortic constriction induced greater increases in heart weight to body weight ratio in WT (by 47%) than CAT+ mice (by 25%) compared with the respective controls (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05). Likewise, the increase in left ventricular wall thickness induced by TAC was significantly attenuated in CAT+ mice (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.05). Cardiac collagen type\u00a0I mRNA expression was greater in WT mice with TAC (by 22%; <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.03), but not in CAT+ mice with TAC, compared with the respective controls. Transverse aortic constriction also induced lesser increases in \u03b2\u2010myosin heavy chain mRNA expression in CAT+ mice compared with WT (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05). Left ventricular systolic pressure after TAC was 36 and 39% greater in WT and CAT+ mice, respectively, compared with the respective controls (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001). Transverse aortic constriction had little effect on left ventricular end\u2010diastolic pressure in both genotypes. Taken together, these data indicate that augmenting endothelial function by overexpression of <jats:sc>l<\/jats:sc>\u2010arginine transport can attenuate pressure\u2010overload\u2010induced cardiac hypertrophy.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep085250","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T09:49:33Z","timestamp":1431337773000},"page":"796-804","source":"Crossref","is-referenced-by-count":5,"title":["Augmented endothelial <scp>l<\/scp>\u2010arginine transport ameliorates pressure\u2010overload\u2010induced cardiac hypertrophy"],"prefix":"10.1113","volume":"100","author":[{"given":"Niwanthi W.","family":"Rajapakse","sequence":"first","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Department of Physiology Monash University Melbourne, Victoria  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