Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_D96EB1412FD4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy.
Périodique
Diabetes
Auteur(s)
Rajesh M., Bátkai S., Kechrid M., Mukhopadhyay P., Lee W.S., Horváth B., Holovac E., Cinar R., Liaudet L., Mackie K., Haskó G., Pacher P.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
61
Numéro
3
Pages
716-727
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Endocannabinoids and cannabinoid 1 (CB(1)) receptors have been implicated in cardiac dysfunction, inflammation, and cell death associated with various forms of shock, heart failure, and atherosclerosis, in addition to their recognized role in the development of various cardiovascular risk factors in obesity/metabolic syndrome and diabetes. In this study, we explored the role of CB(1) receptors in myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death, and interrelated signaling pathways, 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 NH(2)-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs), enhanced inflammation (tumor necrosis factor-α, interleukin-1β, cyclooxygenase 2, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1), increased expression of CB(1), advanced glycation end product (AGE) and angiotensin II type 1 receptors (receptor for advanced glycation end product [RAGE], angiotensin II receptor type 1 [AT(1)R]), p47(phox) NADPH oxidase subunit, β-myosin heavy chain isozyme switch, accumulation of AGE, fibrosis, and decreased expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Pharmacological inhibition or genetic deletion of CB(1) receptors attenuated the diabetes-induced cardiac dysfunction and the above-mentioned pathological alterations. Activation of CB(1) 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, CB(1) receptor inhibition may be beneficial in the treatment of diabetic cardiovascular complications.
Mots-clé
Animals, Apoptosis, Arachidonic Acids/analysis, Diabetic Cardiomyopathies/etiology, Diabetic Cardiomyopathies/physiopathology, Endocannabinoids, Fibrosis, Glycosylation End Products, Advanced/analysis, Heart/physiopathology, Inflammation/etiology, MAP Kinase Signaling System, Male, Mice, Mice, Inbred C57BL, Myocardium/metabolism, Myocardium/pathology, Oxidative Stress, Polyunsaturated Alkamides/analysis, Receptor, Angiotensin, Type 1/analysis, Receptor, Cannabinoid, CB1/antagonists & inhibitors, Receptor, Cannabinoid, CB1/physiology, Ventricular Function, Left
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2013 17:44
Dernière modification de la notice
09/05/2019 2:00
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