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dc.contributor.authorChen, Yu.en_US
dc.date.accessioned2014-10-21T12:33:22Z
dc.date.available2014-10-21T12:33:22Z
dc.date.issued2005en_US
dc.identifier.otherAAINR00970en_US
dc.identifier.urihttp://hdl.handle.net/10222/54700
dc.descriptionHeat shock proteins (Hsps) function in tissue protection through their chaperone activity and by interacting with cell signaling pathways to suppress apoptosis. Heat shock (HS) treatment (core body temperature of 42°C for 15 minutes) with subsequent expression of Hsps, is an effective strategy for protection against oxidative injuries. This thesis examines the protective role of Hsps against Angiotensin (Ang) II-induced cardiovascular inflammatory injury in both animal and cell culture models.en_US
dc.descriptionHS treatment was administered to rats 24 hours before initiation of Ang II infusion. Tail-cuff plethysmography revealed that HS treatment significantly decreased Ang II-induced hypertension. Histological staining of hearts showed that HS treatment reduced Ang II-induced leukocyte infiltration, perivascular and interstitial inflammation and fibrosis. The activation of NF-kappaB in aorta and heart by Ang II was suppressed by HS treatment. HS treatment depleted IKK-alpha and decreased phosphorylated IKK-alpha and suppressed the Ang II-induced depletion of IkappaB-alpha and the accumulation of phosphorylated IkappaB-alpha. HS treatment blocked Ang II induced expression of IL-6 in aorta and heart. In addition, HS treatment significantly suppressed the Ang II-induced activation of pro-inflammatory transcription factors SP-1 and AP-1. Moreover, HS significantly increased anti-inflammatory transcription factor Oct-1 activity that was suppressed by Ang II infusion. Ang II and HS treatment induced high level expression of Hsp27 and Hsp70 and their phosphorylation. Phosphorylated isoforms of Hsp27 and Hsp70 may play an important role interacting with cell signaling pathways to suppress inflammation.en_US
dc.descriptionTo determine whether Hsps regulate inflammation, the heat shock transcription factor-1 (HSF-1) was knocked down with siRNA in vascular smooth muscle cells (VSMCs). The knockdown of HSF-1 suppressed the expression of Hsp27. Ang II induced activation of NF-kappaB and AP-1 in untransfected VSMCs, however in HSF-1 siRNA transfected cells with suppressed expression of Hsp27, Ang II-induced significantly higher activities of NF-kappaB and AP-1.en_US
dc.descriptionThese data suggest that HS treatment and expression of Hsps suppresses inflammation by differentially regulating pro-inflammatory and anti-inflammatory cell signaling pathways, and that the knock down of HSF-1 and suppressed expression of Hsp27 exacerbates Ang II-induced inflammation in VSMCs. This work suggests a direct role for Hsps, and specifically Hsp27 in regulating inflammation.en_US
dc.descriptionThesis (Ph.D.)--Dalhousie University (Canada), 2005.en_US
dc.languageengen_US
dc.publisherDalhousie Universityen_US
dc.publisheren_US
dc.subjectBiology, Animal Physiology.en_US
dc.subjectHealth Sciences, Medicine and Surgery.en_US
dc.subjectHealth Sciences, Pathology.en_US
dc.subjectHealth Sciences, Immunology.en_US
dc.titleHeat shock proteins protect against angiotensin II-induced cardiovascular inflammation.en_US
dc.typetexten_US
dc.contributor.degreePh.D.en_US
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