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Articles by B. H. L Chua
Total Records ( 1 ) for B. H. L Chua
  A Maloyan , J Sayegh , H Osinska , B. H. L Chua and J. Robbins
 

Rationale: Transgenic mice with cardiac specific overexpression of mutated B-crystallin (CryABR120G) display Desmin-related myopathy (DRM) with dilated cardiomyopathy and heart failure. Our previous studies showed the presence of progressive mitochondrial abnormalities and activation of apoptotic cell death in CryABR120G transgenic hearts. However, the role of mitochondrial dysfunction and apoptosis in the overall course of the disease was unclear.

Objective: We tested the hypothesis that prevention of apoptosis would ameliorate CryABR120G pathology and decrease morbidity.

Methods and Results: We crossed CryABR120G mice to transgenic mice with cardiac specific overexpression of Bcl-2. Sustained Bcl-2 overexpression in CryABR120G hearts prolonged CryABR120G transgenic mice survival by 20%. This was associated with decreased mitochondrial abnormalities, restoration of cardiac function, prevention of cardiac hypertrophy, and attenuation of apoptosis. CryABR120G misfolded protein aggregation was significantly reduced in the double transgenic. However, inhibition of apoptotic signaling resulted in the upregulation of autophagy and alternative death pathways, the net result being increased necrosis.

Conclusion: Although Bcl-2 overexpression prolonged life in this DRM model, in the absence of apoptosis, another death pathway was activated.

 
 
 
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