Different Expression and Function of the Endocannabinoid System in Human Epicardial Adipose Tissue in Relation to Heart Disease

• Published in: Canadian journal of cardiology Vol. 29; no. 4; pp. 499 - 509
• Main Authors: Cappellano, Giuseppe, PhD, Uberti, Francesca, PhD, Caimmi, Philippe Primo, MD, PhD, Pietronave, Stefano, PhD, Mary, David A.S.G., MD, Dianzani, Chiara, PhD, Micalizzi, Ezio, MD, Melensi, Matteo, PhD, Boldorini, Renzo, MD, Nicosia, Gabriella, PhD, Crosio, Enrico, MD, Chiocchetti, Annalisa, MD, PhD, Aina, Franco, MD, Prat, Maria, PhD, Dianzani, Umberto, MD, PhD, Vacca, Giovanni, MD, PhD, Ariatti, Cristiano, MD, Grossini, Elena, MD, PhD
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.04.2013
• Subjects: Adipocytes - metabolism; Adipose Tissue - metabolism; Aged; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Aspirin - administration & dosage; Blotting, Western; Cardiovascular; Cyclic AMP-Dependent Protein Kinases - metabolism; Endocannabinoids - metabolism; Enzyme Activation; Ethylenediamines; Female; Free Radical Scavengers; Gene Expression Regulation; Heart Diseases - metabolism; Heart Diseases - physiopathology; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; Pericardium; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Stroke Volume; Sulfanilamides; Up-Regulation
• ISSN: 0828-282X; 1916-7075
• DOI: 10.1016/j.cjca.2012.06.003

Abstract Background The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease. Methods Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue. Results In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics. Conclusions These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.