title: Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes.
abstract: OBJECTIVE
  An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril.
  
  
  METHODS
  Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis.
  
  
  RESULTS
  Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy.
  
  
  CONCLUSIONS
  These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Huynh
authors.forename: H
authors.initials: H
authors.lastname: Kiriazis
authors.forename: X-J
authors.initials: XJ
authors.lastname: Du
authors.forename: J E
authors.initials: JE
authors.lastname: Love
authors.forename: K A
authors.initials: KA
authors.lastname: Jandeleit-Dahm
authors.forename: J M
authors.initials: JM
authors.lastname: Forbes
authors.forename: J R
authors.initials: JR
authors.lastname: McMullen
authors.forename: R H
authors.initials: RH
authors.lastname: Ritchie
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D005260:Female; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017257:Ramipril / Q000627:therapeutic use; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D014815:Vitamins; D013481:Superoxides; D014451:Ubiquinone; D051057:Proto-Oncogene Proteins c-akt; C024989:coenzyme Q10; D017257:Ramipril