Cardiac remodeling and contractile function in acid alpha-glucosidase knockout mice

Area of Science:

• Cardiovascular Research
• Genetics and Disease Modeling
• Lysosomal Storage Disorders

Background:

• Pompe's disease is an autosomal recessive disorder caused by acid alpha-glucosidase deficiency.
• This deficiency leads to glycogen accumulation in cardiac and skeletal muscles.
• Understanding the cardiac impact is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the cardiac phenotype of an acid alpha-glucosidase knockout (KO) mouse model.
• To assess structural and functional cardiac changes in the absence of functional acid alpha-glucosidase.
• To determine the suitability of this KO mouse model for studying Pompe disease pathophysiology and therapeutic strategies.

Main Methods:

• Utilized an acid alpha-glucosidase knockout (KO) mouse model and compared it to wild-type (WT) littermates.
• Performed quantitative analysis of left ventricular (LV) weight-to-body weight ratios.
• Conducted echocardiography to assess LV dimensions and wall thickness.
• Measured LV pressure and contractility (LV dP/dt(max)) under basal and stimulated conditions using different anesthesia protocols.

Main Results:

• KO mice exhibited significantly increased LV weight-to-body weight ratios compared to WT mice.
• Echocardiography revealed increased LV wall thickness and decreased LV lumen diameter in KO mice.
• Cardiac function, assessed by LV dP/dt(max), was significantly impaired in KO mice under various physiological conditions.

Conclusions:

• The acid alpha-glucosidase KO mouse model displays significant cardiac abnormalities, including hypertrophy and dysfunction.
• These findings mirror key cardiac aspects of human infantile Pompe disease.
• This mouse model is a valuable tool for further research into Pompe disease mechanisms and the evaluation of novel therapeutic interventions.