SP 8
PD Dr. med. Oliver Dewald
Department of Cardiac Surgery
University of Bonn Medical Center
Sigmund-Freud-Straße 25
53127 Bonn
Phone: +49 (0)228 287-15109
Fax: +49 (0)228 287-14195
E-mail: o.dewald@uni-bonn.de
CV Dr. Dewald
(57KB)
Dr. med. Daniela Wenzel
Institute of Physiology I
University of Bonn
Sigmund-Freud-Straße 25
53127 Bonn
Phone: +49 (0)228 6885-216
Fax: +49 (0)228 6885-201
E-mail: dwenzel@uni-bonn.de
Homepage Institute of Physiology I
Prof. Dr. med. Bernd K. Fleischmann
Director of the Institute of Physiology I,
University of Bonn
Sigmund-Freud-Straße 25
53127 Bonn
Phone: +49 (0)228 6885-200
Fax: +49 (0)228 6885-201
E-mail: bernd.fleischmann@uni-bonn.de
Homepage Institute of Physiology I
CV Wenzel
(38KB)
CV Fleischmann
(57KB)
The role of the endocannabinoid system in homeostasis and adaptation to pathological conditions in the murine cardiopulmonary system
CB1 and CB2 cannabinoid receptors are widely expressed in the cardiovascular system, but their physiological role during development and in the adult is still unclear. In addition, their modulatory function during cardiac injury and repair is not well understood. Thus, SP8 investigated the role of the ECS in the regulation of vascular tone, heart function and its potential involvement upon cardiac ischemia.
We found that AEA had a prominent effect in the pulmonary circulation, which was not mediated via CB1/CB2 receptors in the isolated perfused lung model. We also investigated the potential role of CB2 receptors in cardiac ischemia and injury. Our data reveal in a model of ischemic cardiomyopathy that CB2 knockout leads to an irreversible loss of cardiomyocytes in contrast to WT mice resulting in a persistent reduction of cardiac pump function. Chimeric mice as well as cell biological assays pinpointed a critical role of the inflammatory response and macrophage function in the ischemic area. Interestingly, after myocardial infarction, a delayed scar formation was found in Cnr2-/- mice. Thus, both of these cardiac injury types provided compelling evidence for a crucial role of CB2 receptors in cardioprotection after myocardial injury.
In the next funding period, we will determine endocannabinoid regulators of pulmonary vascular tone under physiological and pathological conditions. By further experiments we will elucidate the relevance of CB1 receptors in post-ischemic remodeling in clinically relevant models of hypertrophy and myocardial ischemia. These experiments will allow us to identify and dissect the influence of cannabinoids for cardiopulmonary function in pathological processes and aim to gain further mechanistic insights in order to find novel therapeutical targets in fibrogenesis and/or on specific cells types.
Team members:
Michaela Matthey
Tel.: +49 (0)228 6885 216
E-mail: matthey@uni-bonn.de
Dr. med. Georg D. Dürr, post-doc
Tel: +49 (0)228 287-15109
E-mail: dduerr@uni-bonn.de
Jan Heinemann, doctoral student
Tel: +49 (0)228 287-16345
E-mail: jan.heinemann@uni-bonn.de
Kathie Keppel, doctoral student
Tel: +49 (0)228 287-16345
E-mail: k.keppel@googlemail.com
Andreas Feißt, doctoral student
Tel: +49 (0)228 287-16345
E-mail: andreasfeisst@gmx.de
Tim Ommer, doctoral student
Tel: +49 (0)228 287-16345
E-mail: tim-ommer@t-online.de
Christine Peigney, technician
Tel: +49 (0)228 287-16345
E-mail: Christine.Peigney@ukb.uni-bonn.de