Overexpression of dimethylarginine dimethylaminohydrolase 1 protects from angiotensin II-induced cardiac hypertrophy and vascular remodeling

Author:

Kopaliani Irakli1,Jarzebska Natalia234ORCID,Billoff Silke2,Kolouschek Anne2,Martens-Lobenhoffer Jens5ORCID,Bornstein Stefan R.6,Bode-Böger Stefanie M.5,Ragavan Vinitha N.27ORCID,Weiss Norbert26,Mangoni Arduino A.7,Deussen Andreas1,Rodionov Roman N.26

Affiliation:

1. Department of Physiology, Medical Faculty, Dresden University of Technology, Dresden, Germany

2. University Center for Vascular Medicine, Dresden University of Technology, Dresden, Germany

3. Department of Anesthesiology and Critical Care Medicine, University Hospital Dresden, Dresden University of Technology, Dresden, Germany

4. Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

5. Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany

6. University Clinic and Polyclinic III, Dresden University of Technology, Dresden, Germany

7. Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia

Abstract

We showed that overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects from angiotensin II-induced cardiovascular damage, progression of hypertension, and adverse vascular remodeling in vivo. This protective effect strongly depends on the dose and duration of angiotensin II infusion and is associated with decreased levels of asymmetric dimethylarginine (ADMA), preservation of endothelial function, inhibition of cardiovascular inflammation, as well as lower activity of matrix metalloproteinase-2 (MMP2). Our findings are highly clinically relevant, because they suggest that upregulation of DDAH1 might be a promising therapeutic approach against angiotensin II-induced end organ damage.

Funder

MeDDrive program of the Medical Faculty Carl Gustav Carus, Technische Universität Dresden

Deutsche Herzstiftung

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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