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dc.contributor.authorNg, HH
dc.contributor.authorLeo, CH
dc.contributor.authorPrakoso, D
dc.contributor.authorQin, C
dc.contributor.authorRitchie, RH
dc.contributor.authorParry, LJ
dc.date.accessioned2020-12-22T03:41:00Z
dc.date.available2020-12-22T03:41:00Z
dc.date.issued2017-01-09
dc.identifierpii: srep39604
dc.identifier.citationNg, H. H., Leo, C. H., Prakoso, D., Qin, C., Ritchie, R. H. & Parry, L. J. (2017). Serelaxin treatment reverses vascular dysfunction and left ventricular hypertrophy in a mouse model of Type 1 diabetes. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/srep39604.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/257905
dc.description.abstractSerelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups. After 12 weeks of diabetes, sensitivity to the endothelium-dependent agonist acetylcholine (ACh) was reduced in the mesenteric artery. This was accompanied by an enhanced vasoconstrictor prostanoid contribution and a decrease in endothelium-derived hyperpolarisation (EDH)-mediated relaxation. Serelaxin restored endothelial function by increasing nitric oxide (NO)-mediated relaxation but not EDH. It also normalised the contribution of vasoconstrictor prostanoids to endothelial dysfunction and suppressed diabetes-induced hyper-responsiveness of the mesenteric artery to angiotensin II. Similarly, diabetes reduced ACh-evoked NO-mediated relaxation in the aorta which was reversed by serelaxin. In the left ventricle, diabetes promoted apoptosis, hypertrophy and fibrosis; serelaxin treatment reversed this ventricular apoptosis and hypertrophy, but had no effect on fibrosis. In summary, serelaxin reversed diabetes-induced endothelial dysfunction by enhancing NO-mediated relaxation in the mouse vasculature and attenuating left ventricular hypertrophy and apoptosis.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSerelaxin treatment reverses vascular dysfunction and left ventricular hypertrophy in a mouse model of Type 1 diabetes
dc.typeJournal Article
dc.identifier.doi10.1038/srep39604
melbourne.affiliation.departmentUniversity General
melbourne.affiliation.departmentSchool of BioSciences
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.source.titleScientific Reports
melbourne.source.volume7
melbourne.source.issue1
melbourne.identifier.arcLP110200543
dc.rights.licenseCC BY
melbourne.elementsid1177495
melbourne.contributor.authorLeo, Chen
melbourne.contributor.authorQin, Chengxue
melbourne.contributor.authorParry, Laura
melbourne.contributor.authorNg, Hooi Hooi
melbourne.contributor.authorPrakoso, Darnel
melbourne.contributor.authorRitchie, Rebecca
dc.identifier.eissn2045-2322
melbourne.identifier.fundernameidAUST RESEARCH COUNCIL, LP110200543
melbourne.accessrightsOpen Access


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