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Reticulum Endoplasmic Stress and Inflammation Impair Ischemia‐Induced Neovascularization in Type 2 Diabetic Mice
Author(s) -
Matrougui Khalid,
Partyka Megan,
Amin Ali
Publication year - 2011
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.25.1_supplement.1092.3
Subject(s) - medicine , neovascularization , endocrinology , inflammation , ischemia , unfolded protein response , endoplasmic reticulum , angiogenesis , chemistry , biochemistry
Objective Reticulum endoplasmic (ER) stress and inflammation have been reported to be involved in the etiology of type 2 diabetes. In this study, we demonstrated that ER stress and inflammation play a critical role in the altered ischemia‐induced neovascularisation in type 2 diabetic mice. Research/Methods We studied ischemia‐induced neovascularization in the ischemic hind‐limb of 4 weeks old type 2 diabetic (db − /db − ) mice treated with or without ER stress inhibitor (tauroursodeoxycholic acid, TUDCA, 20 mg/Kg/day) and interleukin‐1 receptor antagonist (Anakinra, 0.5 μg/mouse/day) for 4 weeks. Results Blood pressure was similar in all groups. Blood glucose and body weight were reduced in diabetic mice treated with TUDCA. ER stress and inflammation were higher in hind‐limb of diabetic mice, which were reduced by TUDCA and ankinra. The neovascularization and blood flow recovery were significantly attenuated in db − /db − mice compared to control. Interestingly, we demonstrated that the treatment of db − /db − mice by TUDCA or anakinra increased the induction of neovascularization and blood flow recovery compared to non‐treated diabetic mice. Similarly, TUDCA and anakinra re‐established the capillary density, cGMP level, eNOS phosphorylation, VEGF level, and VEGF receptor phosphorylation. Conclusion In the present study, we demonstrated that the induction of ER stress and inflammation impair the ischemia‐induced neovascularization in type 2 diabetic mice likely through the alteration of eNOS and VEGF pathways. Thus, ER stress and inflammation should be potential targets for possible therapeutic strategy to treat impaired neovascularization‐dependent pathologies.