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Effective Treatment of Diabetic Cardiomyopathy and Heart Failure with Reconstituted HDL (Milano) in Mice

Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, 3000 Leuven, Belgium
The Medicines Company (Schweiz) GmbH, CH-8001 Zürich, Switzerland
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(6), 1273;
Received: 13 February 2019 / Revised: 21 February 2019 / Accepted: 8 March 2019 / Published: 13 March 2019
The risk of heart failure (HF) is prominently increased in patients with type 2 diabetes mellitus. The objectives of this study were to establish a murine model of diabetic cardiomyopathy induced by feeding a high-sugar/high-fat (HSHF) diet and to evaluate the effect of reconstituted HDLMilano administration on established HF in this model. The HSHF diet was initiated at the age of 12 weeks and continued for 16 weeks. To investigate the effect of reconstituted HDLMilano on HF, eight intraperitoneal administrations of MDCO-216 (100 mg/kg protein concentration) or of an identical volume of control buffer were executed with a 48-h interval starting at the age of 28 weeks. The HSHF diet-induced obesity, hyperinsulinemia, and type 2 diabetes mellitus. Diabetic cardiomyopathy was present in HSHF diet mice as evidenced by cardiac hypertrophy, increased interstitial and perivascular fibrosis, and decreased myocardial capillary density. Pressure-volume loop analysis indicated the presence of both systolic and diastolic dysfunction and of decreased cardiac output in HSHF diet mice. Treatment with MDCO-216 reversed pathological remodelling and cardiac dysfunction and normalized wet lung weight, indicating effective treatment of HF. No effect of control buffer injection was observed. In conclusion, reconstituted HDLMilano reverses HF in type 2 diabetic mice. View Full-Text
Keywords: type 2 diabetes mellitus; diabetic cardiomyopathy; obesity type 2 diabetes mellitus; diabetic cardiomyopathy; obesity
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Aboumsallem, J.P.; Muthuramu, I.; Mishra, M.; Kempen, H.; De Geest, B. Effective Treatment of Diabetic Cardiomyopathy and Heart Failure with Reconstituted HDL (Milano) in Mice. Int. J. Mol. Sci. 2019, 20, 1273.

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