Effekte des Endocannabinoidrezeptors CB2 auf die myokardiale Protektion

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• 作者：PD Dr. O. Dewald
• 关键词：SchlüsselwörterIschämie ; Reperfusion ; Makrophagen ; Endocannabinoide ; Gewebeumbau
• 刊名：Zeitschrift für Herz-,Thorax- und Gefäßchirurgie
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：30
• 期：6
• 页码：415-419
• 全文大小：
• 刊物主题：Cardiac Surgery; Thoracic Surgery; Vascular Surgery;
• 出版者：Springer Medizin
• ISSN：1435-1277
• 卷排序：30

文摘

There is increasing evidence supporting the importance of the endocannabinoid system and its receptor CB2 in various cardiovascular pathologies. This manuscript summarizes our findings regarding the role of the endocannabinoid system in myocardial protection using experimental models of ischemia under clinically relevant conditions. An important protective role for CB2 receptor could be shown in a murine model of non-infarcted ischemic cardiomyopathy. The underlying mechanisms in vivo included effects on expression of antioxidative enzymes and contractile elements, thus influencing apoptosis of cardiomyocytes. Furthermore, it could be shown that the CB2 receptor regulates inflammatory mediators and differentiation of macrophage subpopulations and thereby resolution of the inflammatory response. These effects also have an impact on the course of postischemic remodeling and fibrosis, where CB2 receptor affects the differentiation of myofibroblasts and collagen deposition. Using an in vivo model of reperfused myocardial infarction we found comparable effects of CB2 receptor on cardiomyocytes and macrophages. In addition, we demonstrated involvement of CB2 receptor in the formation of the infarction border zone via regulation of thrombospondin 1 and thereby the spatial limitation of myocardial damage. Finally, our investigations of the mechanisms in vitro confirmed a strong dependence of cardiomyocyte survival on CB2 receptor and the effects on proinflammatory subpopulations of macrophages during cellular interactions in co-cultures. In conclusion, our findings clearly support the role of the endocannabinoid system acting via CB2 receptor in cardioprotection and remodeling after injury. The potential translational relevance of these results needs to be elucidated in future studies.