Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes

• Published in: Diabetologia Vol. 51; no. 8; pp. 1544 - 1551
• Main Authors: Busche, M. N, Walsh, M. C, McMullen, M. E, Guikema, B. J, Stahl, G. L
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.08.2008; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Cardiac function; Cardiology. Vascular system; Cardiomyopathy; Cardiovascular disease; complement; Complement System Proteins - physiology; Coronary heart disease; Coronary vessels; Crosses, Genetic; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - physiopathology; Disease Models, Animal; Ejection fraction; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose; Heart; Heart attacks; Human Physiology; Hyperglycemia; Insulin; insulin-dependent diabetes mellitus; Internal Medicine; Ischemia; Laboratory animals; Lectins; Male; Mannose-binding lectin; Mannose-Binding Lectin - deficiency; Mannose-Binding Lectin - genetics; Mannose-Binding Lectin - physiology; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia - physiopathology; Myocarditis. Cardiomyopathies; Neutrophils - physiology; Oxidative stress; Reperfusion Injury - physiopathology; United States > US; Complement; Type 1 diabetes; Animal; Mannose-binding lectin; Endocrinopathy; Animal model; Diabetes mellitus; Ischemia reperfusion; Rodentia; Cardiovascular disease; Myocardial ischemia; Mannose; Coronary heart disease; Myocardial disease; Vascular disease; Vertebrata; Mammalia; Mouse; Mannose-binding lectin .Type 1 diabetes
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-008-1044-6

Aims/hypothesis Diabetic patients are at increased risk of cardiomyopathy, acute myocardial infarction and loss of cardiac progenitor cells (CPCs), but the aetiology is poorly understood. We hypothesised a significant role for mannose-binding lectin (MBL) in cardiomyopathies associated with hyperglycaemia. Methods The role of MBL in myocardial ischaemia and reperfusion (MI/R) injury was investigated in wild-type (WT) and MBL-null mice following 2 weeks of streptozotocin-induced hyperglycaemia. Results Hyperglycaemic WT mice presented with significantly decreased left ventricular ejection fractions and increased serum troponin I levels and myocardial inflammation compared with non-diabetic WT mice following MI/R. Hyperglycaemic MBL-null mice or insulin-treated diabetic WT mice were significantly protected from MI/R injury compared with diabetic WT mice. In an additional study using diabetic WT mice, echocardiographic measurements demonstrated signs of dilative cardiomyopathy, whereas heart:body weight ratios suggested hypertrophic cardiac remodelling after 2 weeks of hyperglycaemia. Immunohistochemical analysis of CPCs showed significantly lower numbers in diabetic WT hearts compared with non-diabetic hearts. Insulin-treated diabetic WT or untreated diabetic MBL-null mice were protected from dilative cardiomyopathy, hypertrophic remodelling and loss of CPCs. Conclusions/interpretation These data demonstrate that MBL may play a critical role in diabetic MI/R injury. Further, the absence of MBL appears to inhibit hypertrophic remodelling and hyperglycaemia-induced loss of CPCs after just 2 weeks of hyperglycaemia in mice.