cytochrome-c-t and Hypertrophy--Left-Ventricular

Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Cardiac Output, Low; Caspase 3; Cytochromes c; Disease Models, Animal; Disease Progression; Guinea Pigs; Heart; Hypertrophy, Left Ventricular; Male; Membrane Potential, Mitochondrial; Myocardium; Myocytes, Cardiac; Oxidative Stress

Topics: Animals; Apoptosis; Aurintricarboxylic Acid; Cardiac Output, Low; Caspase 3; Cytochromes c; Guinea Pigs; Hypertrophy, Left Ventricular; Membrane Potential, Mitochondrial; Mitochondrial Proteins; Myocardium; Oxidative Stress

Cytochrome c release from the intermembrane space of mitochondria is one of the triggers of apoptosis. There is no histochemical method available to demonstrate cytochrome c in cryostat sections, possibly because small cytosolic proteins diffuse readily into aqueous fixation media. This report shows that it is possible to demonstrate cytochrome c release in cardiomyocytes in failing myocardium using vapor fixation of cryostat sections and immunohistochemistry. The method is calibrated using sections from gelatin blocks containing known concentrations of cytochrome c. The method is applied to the hypertrophied right ventricular wall of rats in which pulmonary hypertension was induced by monocrotaline. Cytochrome c release is found in a fraction of the cardiomyocytes, leading to a mosaic-staining pattern. Cytochrome c release was found in myocytes over the full range of cross-sectional area (from 1 to 3.9 times control) in the hypertrophied myocardium. Cytosolic cytochrome c concentrations up to 0.4-0.5 mM occur frequently.

Topics: Animals; Cytochromes c; Cytosol; Hypertrophy, Left Ventricular; Immunohistochemistry; Male; Monocrotaline; Myocytes, Cardiac; Rats; Rats, Wistar