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Cannabinoid 1 Receptor Promotes Cardiac Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in Diabetic Cardiomyopathy
Author(s) -
PACHER PAL,
Rajesh Mohanraj,
Batkai Sandor,
Mukhopadhyay Partha,
Lee WenShin,
Horvath Bela,
Cinar Resat,
Liaudet Lucas,
Mackie Ken,
Haskó György
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1128.10
Subject(s) - diabetic cardiomyopathy , cannabinoid receptor , inflammation , medicine , endocannabinoid system , endocrinology , oxidative stress , cardiac fibrosis , fibrosis , advanced glycation end product , cardiomyopathy , receptor , heart failure , glycation , agonist
Endocannabinoids and cannabinoid (CB)1 receptors have been implicated in cardiac dysfunction, inflammation, and cell death associated with various forms of shock, heart failure, and atherosclerosis. We explored the role of CB1 receptors in cardiac dysfunction, inflammation and cell death using a mouse model of type 1 diabetic cardiomyopathy. Diabetic cardiomyopathy was characterized by increased myocardial endocannabinoid anandamide levels, oxidative/nitrative stress, activation of p38/Jun kinase, mitogen‐activated protein kinases, enhanced inflammation, increased expression of CB1, advanced glycation end product and angiotensin II type 1 receptors[AT(1)R], p47(phox), β‐myosin heavy chain isozyme switch, accumulation of AGE, fibrosis, and decreased expression of sarcoplasmic/endoplasmic reticulum Ca(2+)‐ATPase. Pharmacological inhibition or genetic deletion of CB1 receptors attenuated the diabetes‐induced cardiac dysfunction and the above‐mentioned pathological alterations. Activation of CB1 receptors by endocannabinoids may play an important role in the pathogenesis of diabetic cardiomyopathy by facilitating MAPK activation, AT(1)R expression/signaling, AGE accumulation, oxidative/nitrative stress, inflammation, and fibrosis. Conversely, CB1 receptor inhibition may be beneficial in the treatment of diabetic cardiovascular complications.