title: Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes.
abstract: Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 μmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor γ, GW9662 (1 μmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor γ activation.
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
authors.forename: Basma Milad
authors.initials: BM
authors.lastname: Aloud
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
authors.forename: Pema
authors.initials: P
authors.lastname: Raj
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
authors.forename: Kimberley
authors.initials: K
authors.lastname: O'Hara
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
authors.forename: Zongjun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6; College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada R3E 0T5. Electronic address: handerson@sbrc.ca.
authors.forename: Hope D
authors.initials: HD
authors.lastname: Anderson
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6. Electronic address: tnetticadan@sbrc.ca.
authors.forename: Thomas
authors.initials: T
authors.lastname: Netticadan
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000209:etiology / Q000517:prevention & control; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000517:prevention & control; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006943:Hyperglycemia / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007700:Kinetics; D044243:Linoleic Acids, Conjugated / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D004042:Dietary Fats, Unsaturated; D044243:Linoleic Acids, Conjugated; D009124:Muscle Proteins; D047495:PPAR gamma
keywords: Cardiomyocyte hypertrophy; Cardiomyocytes; Conjugated linoleic acid; Contractile dysfunction; Diabetic cardiomyopathy; Hyperglycemia; Rats