title: Insulin treatment attenuates diabetes-increased atherosclerotic intimal lesions and matrix metalloproteinase 9 expression in apolipoprotein E-deficient mice.
abstract: Patients with diabetes mellitus have increased mortality and morbidity of cardiovascular diseases compared with nondiabetic patients. Although clinical studies have shown that effective glycemic control with insulin treatment in patients with type 1 diabetes is associated with reduced cardiovascular events, the underlying mechanisms have not been well understood. In this study, we treated diabetic apolipoprotein E-deficient (apoE-/-) mice with insulin for 20 weeks and studied the effect of insulin treatment on intimal lesion size and matrix metalloproteinase (MMP) 9 expression known to be involved in plaque destabilization. Results showed that insulin treatment, which effectively reduced plasma glucose level in diabetic mice, attenuated diabetes-increased intimal lesion size and significantly inhibited diabetes-increased MMP9 expression, but had no effect on tissue inhibitor of metalloproteinase 1 in atherosclerotic plaques. Furthermore, we observed that insulin treatment did not reduce diabetes-increased macrophage content but inhibited interleukin 6 expression, a stimulator for MMP expression. Taken together, this study has shown for the first time that insulin treatment in diabetic apoE-/- mice changes atherosclerotic lesions and gene expression to a state that favors plaque stability.
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Schuyler
authors.forename: Nga N
authors.initials: NN
authors.lastname: Ta
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology / Q000517:prevention & control; D007328:Insulin / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020298:U937 Cells; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D007328:Insulin; D015850:Interleukin-6; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C501830:Mmp9 protein, mouse