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Antioxid Redox Signal. 2015 Nov 20;23(15):1220-32. doi: 10.1089/ars.2014.6139. Epub 2015 Jun 18.

Specific Mechanisms Underlying Right Heart Failure: The Missing Upregulation of Superoxide Dismutase-2 and Its Decisive Role in Antioxidative Defense.

Author information

1
1 Physiologisches Institut , Justus-Liebig-Universität Gießen, Giessen, Germany .
2
2 Fraunhofer-Institut für Zelltherapie und Immunologie , Leipzig, Germany .
3
3 Pharmahungary Group , Szeged, Hungary .
4
4 Cardiovascular Research Group, Department of Biochemistry, University of Szeged , Szeged, Hungary .
5
5 Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest, Hungary .

Abstract

AIMS:

Research into right ventricular (RV) physiology and identification of pathomechanisms underlying RV failure have been neglected for many years, because function of the RV is often considered less important for overall hemodynamics and maintenance of blood circulation. In view of this, this study focuses on identifying specific adaptive mechanisms of the RV and left ventricle (LV) during a state of chronic nitric oxide (NO) deficiency, one of the main causes of cardiac failure. NO deficiency was induced in rats by L-NAME feeding over a 4 week period. The cardiac remodeling was then characterized separately for the RV/LV using quantitative real-time polymerase chain reaction, histology, and functional measurements.

RESULTS:

Only the RV underwent remodeling that corresponded morphologically and functionally with the pattern of dilated cardiomyopathy. Symptoms in the LV were subtle and consisted primarily of moderate hypertrophy. A massive increase in reactive oxygen species (ROS) (+4.5±0.8-fold, vs. control) and a higher degree of oxidized tropomyosin (+46%±4% vs. control) and peroxynitrite (+32%±2% vs. control) could be identified as the cause of both RV fibrosis and contractile dysfunction. The expression of superoxide dismutase-2 was specifically increased in the LV by 51%±3% and prevented the ROS increase and the corresponding structural and functional remodeling.

INNOVATION:

This study identified the inability of the RV to increase its antioxidant capacity as an important risk factor for developing RV failure.

CONCLUSION:

Unlike the LV, the RV did not display the necessary adaptive mechanisms to cope with increased oxidative stress during a state of chronic NO deficiency.

PMID:
25978844
PMCID:
PMC4657518
DOI:
10.1089/ars.2014.6139
[Indexed for MEDLINE]
Free PMC Article

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