Overexpression of apolipoprotein B attenuates pathologic cardiac remodeling and hypertrophy in response to catecholamines and after myocardial infarction in mice

Abstract

Introduction. The heart produces apolipoprotein (apo) B-containing lipoproteins which enables cardiac export of potentially cardiotoxic lipids. We hypothesized that overexpression of apoB attenuates the pathologic cardiac remodeling and hypertrophic response following pathological stimuli such as chronic adrenergic overstimulation and myocardial infarction (MI). Methods. Cardiac hypertrophy was induced by a chronic infusion of isoproterenol (ISO) 15 mg/kg/day for 3 weeks in human apoB transgenic mice (n = 9) and in non-transgenic wild-type mice (n = 10). As controls, apoB transgenic (n = 10) and wild-type mice (n = 10) saline infusions were used. Transthoracic echocardiography was performed at baseline and after 3 weeks of treatment to evaluate left ventricular (LV) function and morphology. To investigate the effects of expression on postinfarct hypertrophic response we induced MI in apoB transgenic mice (n = 8) and in wild-type controls (n = 11). The hearts were explanted and weighed 6 weeks post MI. Results. At baseline, WT mice had higher BW and LV mass (LVM) compared to the apoB mice. The increase in LV mass and dimensions after 3 weeks of treatment with ISO was significantly lower while systolic function was significantly better in the apoB group. Six weeks post MI the apoB mice had significantly lower heart weight and heart weight to body weight ratio. The infarct size was similar in both groups. Conclusion. Overexpression of apoB attenuates the pathologic remodeling and hypertrophic response to chronic adrenergic stimulation and MI. Our results indicate that cardiac expression of apoB-containing lipoproteins might be an important regulator of myocardial structure and function.

Key Words::

• Hypertrophy
• apolipoprotein B
• myocardial infarction
• cardiac remodeling
• lipids

Acknowledgements

The study was supported by grants from the Swedish Heart and Lung Foundation, Swedish Research Council, ALF Gothenburg. Gothenburg Medical Society, Swedish Medical Society and the Swedish Foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [31].

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.