A mouse model reveals an important role for catecholamine-induced lipotoxicity in the pathogenesis of stress-induced cardiomyopathy

作者：Shao Yangzhen^*; Redfors Bjoern; Stahlman Marcus; Taeng Margareta Scharin; Miljanovic Azra; Moellmann Helge; Troidl Christian; Szardien Sebastian; Hamm Christian; Nef Holger; Boren Jan; Omerovic Elmir

来源：European Journal of Heart Failure, 2013, 15(1): 9-22.

DOI：10.1093/eurjhf/hfs161

• Stress-induced cardiomyopathy
• Takostubo cardiomyopathy
• ApoB lipoprotein
• Adrenergic stimulation
• Lipid metabolism

Stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular dysakinesia) involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC, but the pathomechanisms involved are unknown. We tested the hypothesis that excessive catecholamines cause perturbation of myocardial lipid metabolism and that cardiac lipotoxicity is responsible for the pathogenesis of SIC. %26lt;br%26gt;A single dose injection of isoprenaline (ISO; 400 mg/kg) induced SIC-like regional akinesia in mice. Oil red O staining revealed severe lipid accumulation in the heart 2 h post-ISO. Both intramyocardial lipid accumulation and cardiac function were normalized within 1 week post-ISO and no significant amount of fibrosis was detected. We found that gene expression of lipid importers and exporters (ApoB lipoprotein) was depressed 2 h post-ISO. These results were confirmed by similar findings in SIC patients and in ISO/patient serum-stressed HL-1 cardiomyocytes. Moreover, overexpression of ApoB in the heart was found to protect against the development of ISO-induced cardiac toxicity and cardiac dysfunction. We also found that ISO-induced intramyocardial lipid accumulation caused electrophysiological disturbance and stunning in ISO/patient serum-stressed HL-1 cardiomyocytes. %26lt;br%26gt;The present study demonstrates that lipotoxicity is closely associated with catecholamine-induced myocardial dysfunction, including neurogenic stunning, metabolic stunning, and electrophysiological stunning. Cardiac lipotoxicity may originate from direct inhibition of myocardial ApoB lipoprotein and subsequent decreased lipid export, caused by supraphysiological levels of catecholamines.

• 出版日期2013-1