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Preservation of myocardial fatty acid oxidation prevents diastolic dysfunction in mice subjected to angiotensin II infusion

DC FieldValueLanguage
dc.contributor.author최용선-
dc.date.accessioned2017-10-26T07:46:56Z-
dc.date.available2017-10-26T07:46:56Z-
dc.date.issued2016-
dc.identifier.issn0022-2828-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/152508-
dc.description.abstractRATIONALE: Diastolic dysfunction is a common feature in many heart failure patients with preserved ejection fraction and has been associated with altered myocardial metabolism in hypertensive and diabetic patients. Therefore, metabolic interventions to improve diastolic function are warranted. In mice with a germline cardiac-specific deletion of acetyl CoA carboxylase 2 (ACC2), systolic dysfunction induced by pressure-overload was prevented by maintaining cardiac fatty acid oxidation (FAO). However, it has not been evaluated whether this strategy would prevent the development of diastolic dysfunction in the adult heart. OBJECTIVE: To test the hypothesis that augmenting cardiac FAO is protective against angiotensin II (AngII)-induced diastolic dysfunction in an adult mouse heart. METHODS AND RESULTS: We generated a mouse model to induce cardiac-specific deletion of ACC2 in adult mice. Tamoxifen treatment (20mg/kg/day for 5days) was sufficient to delete ACC2 protein and increase cardiac FAO by 50% in ACC2 flox/flox-MerCreMer+ mice (iKO). After 4weeks of AngII (1.1mg/kg/day), delivered by osmotic mini-pumps, iKO mice showed normalized E/E' and E'/A' ratios compared to AngII treated controls (CON). The prevention of diastolic dysfunction in iKO-AngII was accompanied by maintained FAO and reduced glycolysis and anaplerosis. Furthermore, iKO-AngII hearts had a~50% attenuation of cardiac hypertrophy and fibrosis compared to CON. In addition, maintenance of FAO in iKO hearts suppressed AngII-associated increases in oxidative stress and sustained mitochondrial respiratory complex activities. CONCLUSION: These data demonstrate that impaired FAO is a contributor to the development of diastolic dysfunction induced by AngII. Maintenance of FAO in this model leads to an attenuation of hypertrophy, reduces fibrosis, suppresses increases in oxidative stress, and maintains mitochondrial function. Therefore, targeting mitochondrial FAO is a promising therapeutic strategy for the treatment of diastolic dysfunction.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAcademic Press-
dc.relation.isPartOfJOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAcetyl-CoA Carboxylase/deficiency-
dc.subject.MESHAngiotensin II/administration & dosage*-
dc.subject.MESHAnimals-
dc.subject.MESHCardiomegaly/diagnosis-
dc.subject.MESHCardiomegaly/genetics-
dc.subject.MESHCardiomegaly/metabolism-
dc.subject.MESHCardiomegaly/physiopathology-
dc.subject.MESHDiastole/drug effects-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHEchocardiography-
dc.subject.MESHEnergy Metabolism/genetics-
dc.subject.MESHFatty Acids/metabolism*-
dc.subject.MESHFibrosis-
dc.subject.MESHGene Deletion-
dc.subject.MESHMagnetic Resonance Imaging-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHMyocardium/metabolism*-
dc.subject.MESHMyocardium/pathology-
dc.subject.MESHMyocardium/ultrastructure-
dc.subject.MESHOrganelle Biogenesis-
dc.subject.MESHOxidation-Reduction/drug effects*-
dc.subject.MESHOxidative Stress/genetics-
dc.subject.MESHVentricular Dysfunction/drug therapy-
dc.subject.MESHVentricular Dysfunction/genetics-
dc.subject.MESHVentricular Dysfunction/metabolism*-
dc.titlePreservation of myocardial fatty acid oxidation prevents diastolic dysfunction in mice subjected to angiotensin II infusion-
dc.typeArticle-
dc.publisher.locationEngland-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Anesthesiology and Pain Medicine-
dc.contributor.googleauthorYong Seon Choi-
dc.contributor.googleauthorAna Barbosa Marcondes de Mattos-
dc.contributor.googleauthorDan Shao-
dc.contributor.googleauthorTao Li-
dc.contributor.googleauthorMiranda Nabben-
dc.contributor.googleauthorMaengjo Kim-
dc.contributor.googleauthorWangWang-
dc.contributor.googleauthorRong Tian-
dc.contributor.googleauthorStephen C. Kolwicz-
dc.identifier.doi10.1016/j.yjmcc.2016.09.001-
dc.contributor.localIdA04119-
dc.relation.journalcodeJ01602-
dc.identifier.eissn1095-8584-
dc.identifier.pmid27693463-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0022282816303455?via%3Dihub-
dc.subject.keywordACC2-
dc.subject.keywordCardiac metabolism-
dc.subject.keywordHypertrophy-
dc.subject.keywordLipids-
dc.subject.keywordMyocardium-
dc.subject.keyword[105] Contractile function-
dc.subject.keyword[107] Biochemistry and metabolism-
dc.subject.keyword[140] energy metabolism-
dc.subject.keyword[145] genetically altered mice-
dc.subject.keyword[90] Lipid and lipoprotein metabolism-
dc.contributor.alternativeNameChoi, Yong Seon-
dc.contributor.affiliatedAuthorChoi, Yong Seon-
dc.citation.volume100-
dc.citation.startPage64-
dc.citation.endPage71-
dc.identifier.bibliographicCitationJOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol.100 : 64-71, 2016-
dc.date.modified2017-10-24-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers

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