Abstract without presentation                                                   Mitochondrial Physiology Network 10.9: 100-101 (2005) - download pdf

Mitochondrial dysfunction and oxidative stress in chagasic cardiomyopathy.

Nisha Garg

Depts. Microbiology, Immunology and Pathology, University of Texas Medical Branch, Galveston TX, USA. - nigarg@utmb.edu

Chagasic cardiomyopathy (CCM), is a major public health threat in Latin America and Mexico, and is recognized as an emerging infectious disease in the U.S.  Endomyocardial biopsies from patients in different clinical stages of the disease have suggested that myocardial inflammation and fibrosis play an important role in the pathogenesis of CCM. Because only a few, if any, parasites are detected during progressive CCM, other factors are believed to be involved in activation and/or sustenance of the inflammatory response. These factors are, however, not known.

Our recent studies have provided a new framework for understanding the initiation and progression of CCM. We have shown in experimental models that infection by Trypanosoma cruzi elicits mitochondrial dysfunction that is associated with oxidative modifications and altered activities of the respiratory chain complexes, generation of reactive oxygen species (ROS), and antioxidant/oxidant imbalance in the heart. Further, we have shown that scavenging of ROS diminishes the mitochondrial dysfunction-induced oxidative stress and, subsequently, is effective in limiting the inflammatory responses, and the oxidative damage in the cardiomyocytes and heart tissue of infected mice. These studies suggest that ROS are critical in sustenance of the oxidative stress and elicitation of the pro-inflammatory cytokines in cardiomyocytes and may contribute to tissue fibrosis and cell death associated with chagasic disease development. Our other studies demonstrate the mitochondrial defects and antioxidant/oxidant imbalance are presented in the peripheral blood of the experimental animals and human patients infected by T. cruzi. These data show the effects of the cardiac cellular damage are reflected in the circulatory system. We would discuss the pathophysiological significance of mitochondrial oxidative stress in human chagasic disease development.

1.  Vyatkina G, Bhatia V, Gerstner A, Papaconstantinou J, Garg N (2004). Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development. Biochim Biophys Acta. 1689: 162-73.

2.  Garg N, Gerstner A, Bhatia V, DeFord J, Papaconstantinou J (2004) Gene expression analysis in mitochondria from chagasic mice: alterations in specific metabolic pathways. Biochem. J. 381: 743-752.

3.  Wen J-J, Vyatkina G, Garg N (2004) Oxidative damage and antioxidant defenses during chagasic cardiomyopathy development. Free Rad. Biol. Med. 37: 1821-1833.

4.  Wen J-J, Garg N (2004) Oxidative modification of mitochondrial respiratory complexes in response to the stress of Trypanosoma cruzi infection. Free Rad. Biol. Med. 37: 2072-2081.

5.  Garg N (2005) Mitochondrial dysfunction in chagasic cardiomyopathy. Frontiers in Biosciences 10: 1341-1354.