Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes.
OBJECTIVE
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
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.
Busche
M N
MN
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Thorn 705, Boston, MA 02115, USA.
Walsh
M C
MC
McMullen
M E
ME
Guikema
B J
BJ
Stahl
G L
GL
D000818:Animals; D003165:Complement System Proteins / Q000502:physiology; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*
D037601:Mannose-Binding Lectin; D003165:Complement System Proteins