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Increased Hsp32 Expression and Endothelial Dysfunction in Human
Author(s) -
Rafiee Parvaneh,
Nelson Victoria,
Otterson Mary,
Binion David
Publication year - 2008
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.22.1_supplement.1189.5
Subject(s) - endothelial dysfunction , endocrinology , downregulation and upregulation , immunohistochemistry , oxidative stress , medicine , biology , gene , biochemistry
Endothelial dysfunction in IBD is associated with loss of NO generation and sustained levels of reactive oxygen species (ROS), which is linked to a loss of iNOS gene transcription. Hsp32 is associated with loss of NO generation via inhibition of iNOS gene expression in various disease, but little is known about its expression in IBD. We characterize Hsp32 expression in control and IBD endothelial cells, microvessels and submucosal gut tissues, to define the molecular mechanisms underlying the loss of NO generation, METHODS: Hsp32 and iNOS expression were assessed in freshly resected human gut tissues (normal and IBD) and human intestinal microvascular endothelial cells (HIMEC) by immunohistochemistry, RT‐PCR and Western blotting. RESULTS: Hsp32 expression was significantly increased in Ulcerative colitis (UC) and Crohn's disease (CD) compared to control tissue (n=9 for each group). Whereas the level of iNOS was decreased in the same samples. Strong staining for Hsp32 and a very weak iNOS staining in UC and CD microvessels compared to control tissue was observed. TNF/LPS resulted in increased iNOS expression in HIMEC. CONCLUSION: Increased Hsp32 expression in IBD microvessels may limit NO production leading to endothelial dysfunction. Hsp32 induction during chronic stress is an epigenetic mechanism for altered endothelial gene transcription and homeostasis in human IBD.