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Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure.
J Mol Cell Cardiol 2010; 48(6):1187-93JM

Abstract

Animal studies suggest that the endocannabinoid system (ECS) plays a role in the regulation of myocardial contractility and in the pathogenesis of heart failure. The current study aimed to proof the existence of endocannabinoid receptors on human ventricular myocardium and to determine whether human chronic heart failure (CHF) is associated with changes in endocannabinoid receptor expression and distribution. Expression of cannabinoid receptor 1 (CB1) and cannabinoid receptor (CB2) on human heart was assessed by means of real-time PCR and immunohistochemistry. On healthy human left ventricular myocardium, mRNA transcripts of CB1 and CB2 receptors were expressed in an almost equal proportion. In patients with CHF, mRNA expression of CB1 receptors was shown to be downregulated 0.7-fold (0.7.+/-0.15, n=12, p<0.01), whereas expression of CB2 receptors was upregulated more than 11-fold (11.6+/-4.5; n=12; p<0.005). Corresponding results were obtained by immunohistochemistry. Blood levels of endocannabinoids were significantly elevated (anandamide 3.5-fold (p<0.001); 2-AG 7-fold (p=0.02)) in patients with CHF, as compared to healthy volunteers. Both CB1 and CB2 receptors are present on healthy human left ventricular myocardium in a balanced distribution. Patients suffering from CHF exhibit a shift of the CB1-CB2 receptor ratio towards expression of CB2 receptors combined with significantly elevated peripheral blood levels of endocannabinoids indicating an activation of the ECS. These results might open up new perspectives regarding the role of endocannabinoid signalling in CHF and its potential as a target for pharmacological modulation.

Authors+Show Affiliations

Department of Anesthesiology, Ludwig-Maximilians University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19931541

Citation

Weis, Florian, et al. "Substantially Altered Expression Pattern of Cannabinoid Receptor 2 and Activated Endocannabinoid System in Patients With Severe Heart Failure." Journal of Molecular and Cellular Cardiology, vol. 48, no. 6, 2010, pp. 1187-93.
Weis F, Beiras-Fernandez A, Sodian R, et al. Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure. J Mol Cell Cardiol. 2010;48(6):1187-93.
Weis, F., Beiras-Fernandez, A., Sodian, R., Kaczmarek, I., Reichart, B., Beiras, A., ... Kreth, S. (2010). Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure. Journal of Molecular and Cellular Cardiology, 48(6), pp. 1187-93. doi:10.1016/j.yjmcc.2009.10.025.
Weis F, et al. Substantially Altered Expression Pattern of Cannabinoid Receptor 2 and Activated Endocannabinoid System in Patients With Severe Heart Failure. J Mol Cell Cardiol. 2010;48(6):1187-93. PubMed PMID: 19931541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure. AU - Weis,Florian, AU - Beiras-Fernandez,Andres, AU - Sodian,Ralf, AU - Kaczmarek,Ingo, AU - Reichart,Bruno, AU - Beiras,Andres, AU - Schelling,Gustav, AU - Kreth,Simone, Y1 - 2009/11/26/ PY - 2009/08/29/received PY - 2009/10/27/revised PY - 2009/10/27/accepted PY - 2009/11/26/entrez PY - 2009/11/26/pubmed PY - 2010/11/17/medline SP - 1187 EP - 93 JF - Journal of molecular and cellular cardiology JO - J. Mol. Cell. Cardiol. VL - 48 IS - 6 N2 - Animal studies suggest that the endocannabinoid system (ECS) plays a role in the regulation of myocardial contractility and in the pathogenesis of heart failure. The current study aimed to proof the existence of endocannabinoid receptors on human ventricular myocardium and to determine whether human chronic heart failure (CHF) is associated with changes in endocannabinoid receptor expression and distribution. Expression of cannabinoid receptor 1 (CB1) and cannabinoid receptor (CB2) on human heart was assessed by means of real-time PCR and immunohistochemistry. On healthy human left ventricular myocardium, mRNA transcripts of CB1 and CB2 receptors were expressed in an almost equal proportion. In patients with CHF, mRNA expression of CB1 receptors was shown to be downregulated 0.7-fold (0.7.+/-0.15, n=12, p<0.01), whereas expression of CB2 receptors was upregulated more than 11-fold (11.6+/-4.5; n=12; p<0.005). Corresponding results were obtained by immunohistochemistry. Blood levels of endocannabinoids were significantly elevated (anandamide 3.5-fold (p<0.001); 2-AG 7-fold (p=0.02)) in patients with CHF, as compared to healthy volunteers. Both CB1 and CB2 receptors are present on healthy human left ventricular myocardium in a balanced distribution. Patients suffering from CHF exhibit a shift of the CB1-CB2 receptor ratio towards expression of CB2 receptors combined with significantly elevated peripheral blood levels of endocannabinoids indicating an activation of the ECS. These results might open up new perspectives regarding the role of endocannabinoid signalling in CHF and its potential as a target for pharmacological modulation. SN - 1095-8584 UR - https://www.unboundmedicine.com/medline/citation/19931541/Substantially_altered_expression_pattern_of_cannabinoid_receptor_2_and_activated_endocannabinoid_system_in_patients_with_severe_heart_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(09)00468-4 DB - PRIME DP - Unbound Medicine ER -