title: GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, impairs neovascularization by decreasing endothelial progenitor cell function.
abstract: The number and function of endothelial progenitor cells (EPCs) are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4) mutation) mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS) in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chun-Yao
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Shih
authors.affiliation: Division of Cardiovascular Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsao
authors.affiliation: Department of Computer Science and Information Management, Hung Kuang University, Taichung, Taiwan.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Nen-Chung
authors.initials: NC
authors.lastname: Chang
authors.affiliation: Division of Cardiovascular Surgery, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Sung
authors.initials: CS
authors.lastname: Tsai
authors.affiliation: Division of Cardiovascular Surgery, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsiao-Ya
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Jui-Chi
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Clinical Medical Sciences, China Medical University, Taichung, Taiwan ; Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
mesh_terms: D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000235:genetics*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D018834:Chaperonin 60 / Q000235:genetics* / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D001426:Bacterial Proteins; D018834:Chaperonin 60; D017931:DNA Primers; D052250:Nitric Oxide Synthase Type III