{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:54:02Z","timestamp":1789210442737,"version":"build-2803163510"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T00:00:00Z","timestamp":1476316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007278","name":"Henry Ford Health System","doi-asserted-by":"publisher","award":["A10249"],"award-info":[{"award-number":["A10249"]}],"id":[{"id":"10.13039\/100007278","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0163158","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T13:41:25Z","timestamp":1476366085000},"page":"e0163158","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity"],"prefix":"10.1371","volume":"11","author":[{"given":"Vishal R.","family":"Mali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandar","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajarajan A.","family":"Thandavarayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh S.","family":"Palaniyandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,10,13]]},"reference":[{"issue":"Suppl 2","key":"ref1","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.2337\/diabetes.54.suppl_2.S79","article-title":"Multifaceted therapeutic approaches for a multigenic disease","volume":"54","author":"R Bottino","year":"2005","journal-title":"Diabetes"},{"issue":"3","key":"ref2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1385\/CRIAI:19:3:217","article-title":"New concepts of the etiopathogenesis and treatment of insulin-dependent diabetes mellitus","volume":"19","author":"JF Bach","year":"2000","journal-title":"Clin Rev Allergy Immunol"},{"issue":"Suppl 2","key":"ref3","first-page":"293","article-title":"Advances and controversies in etiopathogenesis of type 1 (insulin-dependent) diabetes mellitus","volume":"11","author":"E Bosi","year":"1998","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.arcmed.2005.01.003","article-title":"Pathogenesis of type 2 diabetes mellitus","volume":"36","author":"JL Leahy","year":"2005","journal-title":"Arch Med Res"},{"issue":"8","key":"ref5","doi-asserted-by":"crossref","first-page":"760","DOI":"10.2337\/diab.26.8.760","article-title":"Relationship of microvascular disease in diabetes to metabolic control","volume":"26","author":"R Engerman","year":"1977","journal-title":"Diabetes"},{"issue":"7","key":"ref6","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.numecd.2013.03.007","article-title":"Fasting and post-prandial glucose and diabetic complication. A meta-analysis","volume":"23","author":"M Monami","year":"2013","journal-title":"Nutr Metab Cardiovasc Dis"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4055\/cios.2013.5.2.118","article-title":"Relations between long-term glycemic control and postoperative wound and infectious complications after total knee arthroplasty in type 2 diabetics","volume":"5","author":"HS Han","year":"2013","journal-title":"Clin Orthop Surg"},{"issue":"5","key":"ref8","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1001\/archinternmed.2011.16","article-title":"Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications cohort","volume":"171","author":"IH de Boer","year":"2011","journal-title":"Arch Intern Med"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/s00125-003-1116-6","article-title":"Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes","volume":"46","author":"SP Laing","year":"2003","journal-title":"Diabetologia"},{"key":"ref10","unstructured":"Geiss LS, Herman HW, Smith PJ. Mortality in non-insulin-dependent diabetes. In: Harris MI, Cowie CC, Stern MP, et al, eds. Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NIH publication 95\u201314681995. p. 233\u201357."},{"issue":"32","key":"ref11","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.2174\/1381612811319320005","article-title":"Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases","volume":"19","author":"TV Fiorentino","year":"2013","journal-title":"Curr Pharm Des"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2337\/diabetes.48.1.1","article-title":"Role of oxidative stress in diabetic complications: a new perspective on an old paradigm","volume":"48","author":"JW Baynes","year":"1999","journal-title":"Diabetes"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: a unifying mechanism","volume":"54","author":"M Brownlee","year":"2005","journal-title":"Diabetes"},{"issue":"3","key":"ref14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/10715762.2013.864761","article-title":"Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease","volume":"48","author":"VR Mali","year":"2014","journal-title":"Free Radic Res"},{"key":"ref15","article-title":"Impairment of aldehyde dehydrogenase-2 by 4-hydroxy-2-nonenal adduct formation and cardiomyocyte hypertrophy in mice fed a high-fat diet and injected with low-dose streptozotocin","author":"NR Mali VR","year":"2014","journal-title":"Experimental Biology and Medicine"},{"issue":"11","key":"ref16","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1006\/jmcc.2001.1454","article-title":"Role of 4-hydroxynonenal in modification of cytochrome c oxidase in ischemia\/reperfused rat heart","volume":"33","author":"J Chen","year":"2001","journal-title":"J Mol Cell Cardiol"},{"issue":"6","key":"ref17","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1021\/tx7000509","article-title":"Enantioselective oxidation of trans-4-hydroxy-2-nonenal is aldehyde dehydrogenase isozyme and Mg2+ dependent","volume":"20","author":"J Brichac","year":"2007","journal-title":"Chemical research in toxicology"},{"issue":"5","key":"ref18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tcm.2009.09.003","article-title":"Aldehyde dehydrogenase 2 in cardiac protection: a new therapeutic target?","volume":"19","author":"GR Budas","year":"2009","journal-title":"Trends Cardiovasc Med"},{"issue":"5895","key":"ref19","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1126\/science.1158554","article-title":"Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart","volume":"321","author":"CH Chen","year":"2008","journal-title":"Science"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1741-7015-10-40","article-title":"Mitochondrial aldehyde dehydrogenase (ALDH2) protects against streptozotocin-induced diabetic cardiomyopathy: role of GSK3beta and mitochondrial function","volume":"10","author":"Y Zhang","year":"2012","journal-title":"BMC Med"},{"issue":"3\u20134","key":"ref21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.2119\/molmed.2010.00114","article-title":"Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats","volume":"17","author":"J Wang","year":"2011","journal-title":"Mol Med"},{"issue":"5","key":"ref22","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.freeradbiomed.2005.10.040","article-title":"Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart","volume":"40","author":"OM Lashin","year":"2006","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1042\/BJ20090934","article-title":"Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal","volume":"424","author":"BG Hill","year":"2009","journal-title":"Biochem J"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1042\/BJ20111255","article-title":"CNGA3 is expressed in inner ear hair cells and binds to an intracellular C-terminus domain of EMILIN1","volume":"443","author":"D Selvakumar","year":"2012","journal-title":"The Biochemical journal"},{"issue":"9","key":"ref25","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3181\/0703-RM-85","article-title":"Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats","volume":"232","author":"SS Palaniyandi","year":"2007","journal-title":"Exp Biol Med (Maywood)"},{"issue":"5","key":"ref26","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1177\/1535370213520109","article-title":"Impairment of aldehyde dehydrogenase-2 by 4-hydroxy-2-nonenal adduct formation and cardiomyocyte hypertrophy in mice fed a high-fat diet and injected with low-dose streptozotocin","volume":"239","author":"VR Mali","year":"2014","journal-title":"Exp Biol Med (Maywood)"},{"issue":"8","key":"ref27","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1111\/j.1582-4934.2010.01174.x","article-title":"PKCbetaII inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses","volume":"15","author":"SS Palaniyandi","year":"2011","journal-title":"J Cell Mol Med"},{"issue":"4","key":"ref28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00418-004-0678-9","article-title":"Hyperglycemia-induced oxidative stress in diabetic complications","volume":"122","author":"GL King","year":"2004","journal-title":"Histochem Cell Biol"},{"key":"ref29","article-title":"Aldehyde dehydrogenase activator attenuates diabetic cardiomyopathy; a role in improving the quality of resident cardiac stem cells? Experimental Biology Meeting","author":"SS Palaniyandi","year":"2010","journal-title":"FASEB J"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/cvr\/cvq192","article-title":"Mitochondrial aldehyde dehydrogenase and cardiac diseases","volume":"88","author":"CH Chen","year":"2010","journal-title":"Cardiovasc Res"},{"issue":"5","key":"ref31","doi-asserted-by":"crossref","first-page":"e000779","DOI":"10.1161\/JAHA.113.000779","article-title":"Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK\/p53 pathway in mice","volume":"3","author":"A Sun","year":"2014","journal-title":"J Am Heart Assoc"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1161\/ATVBAHA.115.306012","article-title":"Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic Ischemia: Potential Impact on the Development of Coronary Collateral Circulation","volume":"35","author":"X Liu","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"19","key":"ref33","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1161\/CIRCULATIONAHA.114.013120","article-title":"East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome","volume":"131","author":"Y Mizuno","year":"2015","journal-title":"Circulation"},{"key":"ref34","article-title":"Mitochondrial aldehyde dehydrogenase 2 deficiency aggravates energy metabolism disturbance and diastolic dysfunction in diabetic mice","author":"C Wang","year":"2016","journal-title":"J Mol Med (Berl)"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"H1343","DOI":"10.1152\/ajpheart.01200.2004","article-title":"PKC-{epsilon}-dependent survival signals in diabetic hearts","volume":"289","author":"A Malhotra","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.bbadis.2003.11.007","article-title":"Oxidatively damaged proteins of heart mitochondrial electron transport complexes","volume":"1688","author":"KB Choksi","year":"2004","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"ref37","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1016\/j.ddmec.2010.07.002","article-title":"Regulation of mitochondrial processes: a target for heart failure","volume":"7","author":"SS Palaniyandi","year":"2010","journal-title":"Drug Discov Today Dis Mech"},{"issue":"12","key":"ref38","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1073\/pnas.96.12.6689","article-title":"Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase","volume":"96","author":"DT Lucas","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1021\/bi971958i","article-title":"Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal","volume":"37","author":"KM Humphries","year":"1998","journal-title":"Biochemistry"},{"issue":"1","key":"ref40","first-page":"H192","article-title":"Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart","volume":"271","author":"CE Flarsheim","year":"1996","journal-title":"Am J Physiol"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12012-011-9128-9","article-title":"Curcumin protects from cardiac reperfusion damage by attenuation of oxidant stress and mitochondrial dysfunction","volume":"11","author":"A Gonzalez-Salazar","year":"2011","journal-title":"Cardiovasc Toxicol"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cardiores.2006.01.016","article-title":"Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole","volume":"70","author":"F Di Lisa","year":"2006","journal-title":"Cardiovasc Res"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jacc.2005.09.050","article-title":"The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy","volume":"47","author":"J Asbun","year":"2006","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"716","DOI":"10.2337\/db11-0477","article-title":"Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy","volume":"61","author":"M Rajesh","year":"2012","journal-title":"Diabetes"},{"issue":"5","key":"ref45","doi-asserted-by":"crossref","first-page":"R223","DOI":"10.1186\/ar4062","article-title":"Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis","volume":"14","author":"Q Shi","year":"2012","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"ref46","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s12265-012-9405-4","article-title":"Crosstalk between the renin-angiotensin system and the advance glycation end product axis in the heart: role of the cardiac fibroblast","volume":"5","author":"KG Yamazaki","year":"2012","journal-title":"Journal of cardiovascular translational research"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0163158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T11:21:48Z","timestamp":1568460108000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0163158"}},"subtitle":[],"editor":[{"given":"Suresh Kumar","family":"Verma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10,13]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0163158","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,13]]}}}