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Platelet‐Endothelial Association with Fibrinogen/Fibrin, Coupled with Oxidative Stress, Protein Nitrosylation, and Fibrosis may underlie Pulmonary Endothelial Cell Dysfunction in a Mouse Model of Type 1 Diabetes
Author(s) -
Roberts Andrew,
Jagadapillai Rekha,
Dixon James,
Tan Yi,
Cai Lu,
Gozal Evelyne
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.634.8
Subject(s) - pulmonary fibrosis , medicine , sirius red , oxidative stress , endocrinology , endothelial dysfunction , fibrosis , nitric oxide , diabetes mellitus , fibrinogen , lung
Diabetes is characterized by inflammation and abnormal microvascular function. Pulmonary complications, although not well characterized, have been reported in diabetic patients. We hypothesized that oxidative stress, altered nitric oxide synthesis and enhanced fibrinogen‐endothelial interaction in the diabetic lung may underlie pulmonary vascular dysfunction. FVB mice, 8‐10 weeks‐old, were injected with streptozocin (FVB DM; 50mg/kg for 5 days) to induce type 1 diabetes, or with vehicle (FVB Ctr). Lung superoxide formation (DHE) and protein nitrosylation (3‐NT) were assessed after 5 months as indicators of oxidative stress, and type I and type III collagen deposition (Sirius Red) as a marker of pulmonary fibrosis. Superoxide production (152.74 ± 9.11 DM vs. 110.23 ± 3.34 Ctr) and collagen deposition (259.47 ± 8.9 DM vs. 192.89 ± 17.68 Ctr) significantly increased in FVB‐DM (p<0.05; n=3). Protein nitrosylation was elevated, but did not reach significance (102.61 ± 19.18 DM vs. 84.97 ± 10.48 Ctr). Fibrinogen, endothelial cell (CD‐31) and platelet (CD‐61) interactions, assessed by immunochemical staining, showed enhanced expression and co‐localization in FVB DM mice. These data indicate that the lung may be an important target of diabetes‐induced inflammatory injury, inducing decreased nitric oxide bioavailability, significant pulmonary microvascular injury and fibrosis. We conclude that diabetic pulmonary complications could lead to ventilation‐perfusion abnormalities that would exacerbate systemic complications of diabetes.