title: Absence of mannose-binding lectin prevents hyperglycemic cardiovascular complications.
abstract: Diabetes, stress, pharmaceuticals, surgery, and physical trauma can lead to hyperglycemic conditions. A consistent relationship has been found between chronic inflammation and the cardiovascular complications of hyperglycemia. We hypothesized that cardiomyopathy and vasculopathy resulting from acute hyperglycemia are dependent on mannose-binding lectin (MBL) and lectin complement pathway activation. Hyperglycemia was induced in wild-type (WT) C57BL/6 and MBL-null mice after streptozotocin administration. Echocardiographic data and tissue samples were collected after 4, 7, or 14 days of acute hyperglycemia. Hyperglycemic WT mice demonstrated dilated cardiomyopathy with significantly increased short and long axis area measurements during systole and diastole compared to hyperglycemic MBL-null mice. The EC(50) for acetylcholine-induced relaxation of mesenteric arterioles in WT mice after 4 days of hyperglycemia demonstrated a significant loss of nitric oxide-mediated relaxation compared to normoglycemic WT or hyperglycemic MBL-null mice. Myocardial histochemistry and Western blot analysis revealed a significant influx of macrophages, altered morphology, and increased elastin and collagen deposition in hyperglycemic WT hearts compared to MBL-null hearts. Serum transforming growth factor-β1 levels were significantly lower in hyperglycemic MBL-null compared to WT mice, suggesting decreased profibrotic signaling. Together, these data suggest that MBL and the lectin complement pathway play a significant role in vascular dysfunction and cardiomyopathy after acute hyperglycemia.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Vasile I
authors.initials: VI
authors.lastname: Pavlov
authors.forename: Laura R
authors.initials: LR
authors.lastname: La Bonte
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Markiewski
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003167:Complement Activation / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006943:Hyperglycemia / Q000150:complications* / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D037601:Mannose-Binding Lectin; D014665:Vasodilator Agents; D000109:Acetylcholine
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