Messmann, Rebecca and Dietl, Alexander and Wagner, Stefan and Domenig, Oliver and Jungbauer, Carsten and Luchner, Andreas and Maier, Lars S. and Schopka, Simon and Hirt, Stephan and Schmid, Christof and Birner, Christoph (2020) Alterations of the renin angiotensin system in human end-stage heart failure before and after mechanical cardiac unloading by LVAD support. MOLECULAR AND CELLULAR BIOCHEMISTRY, 472 (1-2). pp. 79-94. ISSN 0300-8177, 1573-4919
Full text not available from this repository. (Request a copy)Abstract
Heart transplantation is often an unrealizable therapeutic option for end-stage heart failure, which is why mechanical left ventricular assist devices (LVADs) become an increasingly important therapeutic alternative. Currently, there is a lack of information about molecular mechanisms which are influenced by LVADs, particularly regarding the pathophysiologically critical renin angiotensin system (RAS). We, therefore, determined regulation patterns of key components of the RAS and the beta-arrestin signaling pathways in left ventricular (LV) tissue specimens from 8 patients with end-stage ischemic cardiomyopathy (ICM) and 12 patients with terminal dilated cardiomyopathy (DCM) before and after LVAD implantation and compared them with non-failing (NF) left ventricular tissue samples: AT1R, AT2R, ACE, ACE2, MasR, and ADAM17 were analyzed by polymerase chain reaction. ERK, phosphorylated ERK, p38, phosphorylated p38, JNK, phosphorylated JNK, GRK2, beta-arrestin 2, PI3K, Akt, and phosphorylated Akt were determined by Western blot analysis. Angiotensin I and Angiotensin II were quantified by mass spectrometry. Patients were predominantly middle-aged (53 +/- 10 years) men with severely impaired LV function (LVEF 19 +/- 8%), when receiving LVAD therapy for a mean duration of 331 +/- 317 days. Baseline characteristics did not differ significantly between ICM and DCM patients. By comparing failing with non-failing left ventricles, i.e., before LVAD implantation, a downregulation of AT1R, AT2R, and MasR and an upregulation of ACE, ACE2, GRK, beta-arrestin, ERK, PI3K, and Akt were seen. Following LVAD support, then angiotensin I, ACE2, GRK, and beta-arrestin were downregulated and AT2R, JNK, and p38 were upregulated. ACE, angiotensin II, AT1R, ADAM17, MasR, ERK, PI3K, and Akt remained unchanged. Some regulation patterns were influenced by the underlying etiology of heart failure, the severity of LV dysfunction at baseline, and the duration of LVAD therapy. Key components of the RAS and beta-arrestin signaling pathways were divergently altered in failing left ventricles both before and after LVAD implantation, whereas a remarkable fraction remained unchanged. This indicates a rather incomplete molecular reverse remodeling, whose functional relevance has to be further evaluated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ASSIST DEVICE SUPPORT; DESTINATION THERAPY; CIRCULATORY SUPPORT; GENE-EXPRESSION; II RECEPTOR; MYOCARDIUM; HYPERTROPHY; INHIBITION; REGRESSION; PULSATILE; Heart failure; LVAD; Renin angiotensin system |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 07:00 |
| Last Modified: | 22 Mar 2021 07:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44371 |
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