The effects of Chlamydophila pneumoniae infection on vasorelaxant responses

• Main Authors: Chia-Yu Chen, 陳家羽
• Other Authors: Tsun-Mei Lin
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/31726577679714002315

碩士 === 國立成功大學 === 醫學檢驗生物技術學系碩博士班 === 97 === Impaired vasorelaxant response is an important feature of early atherosclerosis. Increasing evidences suggest that Chlamydophila pneumoniae (C. pneumoniae) infection participates in atherosclerosis and its clinical sequelae. However, it is still unclear how C. pneumoniae infection contributes to the pathogenesis of atherosclerosis especially in the early stage. Specific aim of this study is to explore the molecular mechanisms of C. pneumoniae infection on vasorelaxant responses in vivo and in vitro. Male Wistar rats were inoculated intranasally with C. pneumoniae or saline every week over a 3-week period. The rats were sacrificed at the 4th week after the first inoculation and the thoracic aortas were isolated analyzing vasorelaxant responses to the vasodilators, acetylcholine (ACh) and insulin-like growth factor-1 (IGF-1). Our results showed that both ACh- and IGF-1-evoked vasorelaxations were attenuated in the C. pneumoniae-infected rats with an endothelium-dependent manner. After pre-administration with an inhibitor of nitric oxide synthase (NOS), N-nitro-L-arginine methyl ester, but not with which of prostacyclin, indomethacin, the altered ACh- or IGF-1-induced vasorelaxations were abolished. We also demonstrated C. pneumoniae diminished endothelial NOS (eNOS) phosphorylation with an Akt-dependent pathway in human umbilical vein endothelial cells (HUVECs). The heat-sensitive protein from C. pneumoniae proliferation suppressing the eNOS activation was demonstrated to be chlamydial heat shock protein 60 (cHSP60) through TLR4 on HUVECs. The role of cHSP60 was also verified by higher anti-cHSP60 in the plasma of C. pneumoniae-infected rats. To a greater extent, C. pneumoniae infection suppressed eNOS activity by cHSP60 through TLR4 and resulted in the impaired vasorelaxant responses.