title: The GroEL protein of Porphyromonas gingivalis regulates atherogenic phenomena in endothelial cells mediated by upregulating toll-like receptor 4 expression.
abstract: Porphyromonas gingivalis (P. gingivalis) is a bacterial species that causes periodontitis. GroEL from P. gingivalis may possess biological activity and may be involved in the destruction of periodontal tissues. However, it is unclear whether P. gingivalis GroEL enhances the appearance of atherogenic phenomena in endothelial cells and vessels. Here, we constructed recombinant GroEL from P. gingivalis to investigate its effects in human coronary artery endothelial cells (HCAECs) in vitro and on aortas of high-cholesterol (HC)-fed B57BL/6 and B57BL/6-Tlr4(lps-del) mice in vivo. The results showed that GroEL impaired tube-formation capacity under non-cytotoxic conditions in HCAECs. GroEL increased THP-1 cell/HCAEC adhesion by increasing the expression of intracellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in endothelial cells. Additionally, GroEL increased DiI-oxidized low density lipoprotein (oxLDL) uptake, which may be mediated by elevated lectin-like oxLDL receptor (LOX)-1 but not scavenger receptor expressed by endothelial cells (SREC) and scavenger receptor class B1 (SR-B1) expression. Furthermore, GroEL interacts with toll-like receptor 4 (TLR4) and plays a causal role in atherogenesis in HCAECs. Human antigen R (HuR), an RNA-binding protein with a high affinity for the 3' untranslated region (3'UTR) of TLR4 mRNA, contributes to the up-regulation of TLR4 induced by GroEL in HCAECs. In a GroEL animal administration study, GroEL elevated ICAM-1, VCAM-1, LOX-1 and TLR4 expression in the aortas of HC diet-fed wild C57BL/6 but not C57BL/6-Tlr4(lps-del) mice. Taken together, our findings suggest that P. gingivalis GroEL may contribute to cardiovascular disorders by affecting TLR4 expression.
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University HospitalTaipei, Taiwan.
authors.forename: Chun-Yao
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University HospitalTaipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Shih
authors.affiliation: Division of Cardiovascular Surgery, Taipei Medical University Hospital Taipei.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsao
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Institute of Oral Biology, National Yang-Ming UniversityTaipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Division of Cardiovascular Surgery, Taipei Veterans General Hospital Taipei, Taiwan.
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Shih
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University HospitalTaipei, Taiwan.
authors.forename: Kuang-Hsing
authors.initials: KH
authors.lastname: Chiang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Chi-Kun
authors.initials: CK
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University HospitalTaipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
keywords: GroEL; Porphyromonas gingivalis; atherosclerosis