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Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy
Insights
This study reveals an imbalanced antioxidant enzyme activity in porcine hearts with hypertrophic cardiomyopathy (HCM). Elevated copper, zinc-superoxide dismutase (Cu,Zn-SOD) and reduced catalase (CAT) correlate with disease severity and oxidative stress.
Area of Science:
- Cardiology
- Biochemistry
- Animal Models
Background:
- Hypertrophic cardiomyopathy (HCM) is a cardiac disease.
- Porcine models with naturally occurring HCM exhibit similarities to human conditions, including myocardial ischemia.
- Oxidative stress is implicated in ischemic injury.
Purpose of the Study:
- To investigate the expression and activity of endogenous antioxidant enzymes in porcine hearts with and without HCM.
- To determine the relationship between antioxidant enzyme profiles and the severity of cardiac hypertrophy and oxidative damage.
Main Methods:
- Developed a porcine model of naturally occurring HCM.
- Measured activities of antioxidant enzymes, specifically Cu,Zn-superoxide dismutase (SOD) and catalase (CAT), in myocardial tissues.
- Assessed lipid damage and correlated enzyme activity with hypertrophy severity.
Main Results:
- Significantly increased Cu,Zn-SOD activity and decreased CAT activity were observed in HCM hearts compared to normal hearts.
- The ratio of SOD to CAT activity was significantly higher in HCM hearts.
- Elevated SOD/CAT ratios correlated with the severity of cardiac hypertrophy and increased lipid damage.
Conclusions:
- An imbalanced antioxidant enzyme profile, characterized by elevated Cu,Zn-SOD and reduced CAT, is present in porcine HCM hearts.
- This imbalance may contribute to oxidative stress and disease progression in HCM.
- Further research is needed to elucidate the pathogenic role of imbalanced antioxidant enzymes in HCM.
Abstract:
We have recently developed a porcine model with naturally occurring hypertrophic cardiomyopathy (HCM). Similar to humans, occluded intramural coronary artery and damaged mitochondria are frequently observed in these animals in which the disease is thought to be associated with the local ischemia of myocardium. In view of antioxidant functions involved in the ischemic injury, we measured the expression of endogenous antioxidant enzymes in the tissues with and without HCM. The results showed a significant increase of Cu,Zn-superoxide dismutase (SOD), but not Mn-SOD, and decrease of catalase (CAT) activities in the various areas of HCM hearts. It was demonstrated that SOD/CAT ratios in the HCM hearts were significantly higher than those in normals and were found to be dramatically correlated with the severity of cardiac hypertrophy. The altered SOD/CAT ratio was also consistent with increase in lipid damage. We hypothesize that the elevated SOD combined with an inadequate amount of H2O2 scavenging enzyme may lead HCM heart at oxidative stress risk. However, the pathogenic role of imbalanced antioxidant enzyme needs to be further explored.