title: Role of metabolic environment on nitric oxide mediated inhibition of neointimal hyperplasia in type 1 and type 2 diabetes.
abstract: Nitric oxide (NO) is well known to inhibit neointimal hyperplasia following arterial injury. Previously, we reported that NO was more effective at inhibiting neointimal hyperplasia in a type 2 diabetic environment than control. We also found that NO was ineffective in an uncontrolled type 1 diabetic environment; however, insulin restored the efficacy of NO. Thus, the goal of this study was to more closely evaluate the effect of insulin and glucose on the efficacy of NO at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments using different doses of insulin as well as pioglitazone. Type 1 diabetes was induced in male lean Zucker (LZ) rats with streptozotocin (60 mg/kg IP). Groups included control, moderate glucose control, and tight glucose control. Zucker diabetic fatty (ZDF) rats fed Purina 5008 chow were used as a type 2 diabetic model. Groups included no therapy, insulin therapy, or pioglitazone therapy. After 4 weeks of maintaining group assignments, the carotid artery injury model was performed. Treatment groups included: control, injury and injury plus NO. 2 weeks following arterial injury, in the type 1 diabetic rats, NO most effectively reduced the neointimal area in the moderate and tightly controlled groups (81% and 88% vs. 33%, respectively, p=0.01). In type 2 diabetic rats, the metabolic environment had no impact on the efficacy of NO (81-82% reduction for all groups). Thus, in this study, we show NO is effective at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments. A greater understanding of how the metabolic environment may impact the efficacy of NO may lead to the development of more effective NO-based therapies for patients with diabetes.
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Monica P
authors: MP
authors: Rodriguez
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Zachary M
authors: ZM
authors: Emond
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Zheng
authors: Z
authors: Wang
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Janet
authors: J
authors: Martinez
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Qun
authors: Q
authors: Jiang
authors: Division of Vascular Surgery, and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Melina R
authors: MR
authors: Kibbe
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000378:metabolism; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000378:metabolism; D008297:Male; D058426:Neointima / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D009569:Nitric Oxide; D006136:GTP Cyclohydrolase
keywords: Diabetes; Insulin; Neointimal hyperplasia; Nitric oxide