Nai-Wen Tsao

Taipei Medical University Hospital, T’ai-pei, Taipei, Taiwan

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Publications (30)69.66 Total impact

  • [Show abstract] [Hide abstract] 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.
    No preview · Article · Feb 2016 · American Journal of Translational Research
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    [Show abstract] [Hide abstract] ABSTRACT: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are used to reduce cholesterol biosynthesis in the liver. Accordingly, statins regulate nitric oxide (NO) and glutamate metabolism, inflammation, angiogenesis, immunity and endothelial progenitor cells (EPCs) functions. The function of EPCs are regulated by stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β), etc. Even though the pharmacologic mechanisms by which statins affect the neovasculogenesis of circulating EPCs, it is still unknown whether statins affect the EPCs function through the regulation of CXCR4, a SDF-1 receptor expression. Therefore, we desired to explore the effects of statins on CXCR4 expression in EPC-mediated neovascularization by in vitro and in vivo analyses. In animal studies, we analyzed the effects of atorvastatin or rosuvastatin treatments in recovery of capillary density and blood flow, the expression of vWF and CXCR4 at ischemia sites in hindlimb ischemia ICR mice. Additionally, we analyzed whether the atorvastatin or rosuvastatin treatments increased the mobilization, homing, and CXCR4 expression of EPCs in hindlimb ischemia ICR mice that underwent bone marrow transplantation. The results indicated that statins treatment led to significantly more CXCR4-positive endothelial progenitor cells incorporated into ischemic sites and in the blood compared with control mice. In vivo, we isolated human EPCs and analyzed the effect of statins treatment on the vasculogenic ability of EPCs and the expression of CXCR4. Compared with the control groups, the neovascularization ability of EPCs was significantly improved in the atorvastatin or rosuvastatin group; this improvement was dependent on CXCR4 up-regulation. The efficacy of statins on improving EPC neovascularization was related to the SDF-1α/CXCR4 axis and might be regulated by the NO. In conclusion, atorvastatin and rosuvastatin improved neovascularization in hindlimb ischemia mice; this effect may have been mediated by increased CXCR4 expression in EPCs.
    Full-text · Article · Aug 2015 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Late-outgrowth endothelial progenitor cells (EPCs) are stress-resistant and responsible for reparative functions in the cardiovascular system. Oxidized-LDL (oxLDL) plays a critical role in cardiovascular disease pathogenesis. However, it is largely unknown what the impacts of oxLDL are on late-outgrowth EPCs. This study aimed to investigate the concentration-related effects of oxLDL on EPC functions and related angiogenesis, in vitro and in vivo. In this study, early and late-outgrowth EPCs were generated from circulating human mononuclear cells. oxLDL may regulate EPC vasculogenic function via the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Lower concentrations (5 μg/mL) of oxLDL can potentiate EPC tube formation in vitro and in vivo by activating eNOS mechanisms, which are mediated by p38 MAPK- and SAPK/JNK-related pathways. Higher concentrations of oxLDL (10-50 μg/mL) impaired EPC function via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways and consequent inhibition of eNOS activity, which could be reversed by anti-oxidants (diphenylene iodonium and apocynin) and gp91phox siRNA. In conclusion, oxLDL has concentration-dependent biphasic effects on human late-outgrowth EPC tube formation in vitro and in vivo.
    Full-text · Article · May 2015 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Porphyromonas gingivalis is a major periodontal pathogen that contains a variety of virulence factors. The antibody titer to P. gingivalis GroEL, a homologue of HSP60, is significantly higher in periodontitis patients than in healthy control subjects, suggesting that P. gingivalis GroEL is a potential stimulator of periodontal disease. However, the specific role of GroEL in periodontal disease remains unclear. Here, we investigated the effect of P. gingivalis GroEL on human periodontal ligament (PDL) cells in vitro, as well as its effect on alveolar bone resorption in rats in vivo. First, we found that stimulation of PDL cells with recombinant GroEL increased the secretion of the bone resorption-associated cytokines interleukin (IL)-6 and IL-8, potentially via NF-κB activation. Furthermore, GroEL could effectively stimulate PDL cell migration, possibly through activation of integrin α1 and α2 mRNA expression as well as cytoskeletal reorganization. Additionally, GroEL may be involved in osteoclastogenesis via receptor activator of nuclear factor κ-B ligand (RANKL) activation and alkaline phosphatase (ALP) mRNA inhibition in PDL cells. Finally, we inoculated GroEL into rat gingiva, and the results of microcomputed tomography (micro-CT) and histomorphometric assays indicated that the administration of GroEL significantly increased inflammation and bone loss. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to osteoclastogenesis of PDL cells and resulting in periodontal disease with alveolar bone resorption.
    Full-text · Article · Jul 2014 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Continuous renal replacement therapy (CRRT) may benefit patients requiring extracorporeal membrane oxygenation (ECMO). However, the clinical benefits and timing of CRRT have not been fully elucidated for these patients. Methods: This study was conducted retrospectively at the Taipei Medical University Hospital between January 2008 and December 2010. We included patients who had Acute Kidney Injury Network (AKIN) stage 3 disease at the initiation of ECMO and subsequently underwent CRRT. We excluded patients aged <18 years or those who were chronic dialysis patients. Early dialysis was defined as receiving CRRT <24 h after the initiation of ECMO. The primary outcome was mortality before weaning from ECMO. Results: The median age of the 15 patients included in the study was 72 years. The median interval between ECMO and CRRT was 16 h. No significant difference in survival was observed between the early- and late-dialysis patients (p = 0.58, log-rank test). However, a trend toward a shorter mean duration of ECMO therapy was observed in the early-dialysis patients (124 vs. 169 h, p = 0.16). The median follow-up glomerular filtration rate for the survivors was 38.9 ml/min/1.73 m2. Conclusion: No survival benefit is conferred by the use of CRRT within 24 h after initiating ECMO in patients with severe acute kidney injury according to AKIN criteria.
    Full-text · Article · Jul 2014 · CardioRenal Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background/Purpose Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. Methods A human promonocytic (macrophage-like) cell line (U937) was exposed to graduated concentrations of Ni2+in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. Results Ni caused U937 cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni2+ (>240 μM) significantly induced cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive cells according to flow cytometric surveillance and triggered apoptotic cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni2+ treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni2+-induced U937 cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni2+ ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 μM Ni2+-treated medium. Conclusion Our results demonstrated that a high concentration of Ni ions causes apoptotic cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices.
    No preview · Article · May 2014 · Journal of the Formosan Medical Association
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    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Dec 2013 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Background We evaluated the predictive value of traditional Framingham risk score (FRS) for subclinical coronary plaque detected by computed tomography coronary angiogram (CTCA) in asymptomatic patients with zero to low coronary artery calcium (CAC) scores. Methods We assessed 167 asymptomatic Taiwanese patients (mean age, 57 ± 11.2 years) who underwent CTCA as part of a health check-up evaluation, and examined the association between FRS, serum biomarkers, and coronary plaque assessed by CTCA. Results Of 127 patients with CAC scores between <100 and zero, 55 (43%) had coronary artery atheroma. Among the possible predictors of coronary atherosclerosis, FRS was an independent predictor (relative risk 1.25, 95% confidence interval 1.05–1.50, p < 0.05). A receiver-operating-characteristic curve analysis revealed that FRS is a good indicator of the presence of coronary plaque. The area under the FRS curve was 0.70 (p < 0.001), with 62% sensitivity and 63% specificity. Furthermore, adding high-sensitivity C-reactive protein with FRS provides limited advantages for predicting the presence of coronary plaque over FRS alone. Conclusion FRS could be helpful for physicians in assessing coronary artery disease risk for more targeted therapy among patients with zero to low CAC scores.
    Full-text · Article · Dec 2013 · Journal of Experimental and Clinical Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Current treatment modalities for critical limb ischemia (CLI) are of limited benefit; therefore, advances in therapeutic vasculogenesis may open an important new avenue for the treatment of CLI. This study examines the therapeutic potential of the DPP-4 inhibitor MK-0626 as a regulator of vasculogenesis in vivo. MK-0626 was administered daily to C57CL/B6 mice and eGFP-labeled bone marrow-transplanted ICR mice that had undergone hind limb ischemia surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neo-vasculogenesis and the number of circulating endothelial progenitor cells (EPCs), respectively. Cell surface markers of EPCs and the level of endothelial nitric oxide synthase (eNOS) were studied in the vessels. Mice that received MK-0626 had an elevated level of glucagon-like peptide-1 (GLP-1) and a decreased level of dipeptidyl peptidase-4 (DPP-4) in their plasma, in addition to an ischemia-induced increase in the level of stromal cell-derived factor-1 (SDF-1). In C57CL/B6 mice, blood flow in the ischemic limb was significantly improved by treatment with MK-0626. The number of circulating EPCs and both the synthesis and phosphorylation of eNOS were also increased in ischemic thigh muscle after MK-0626 treatment. In contrast, similar effects of MK-0626 were not observed in B6.129P2-Nos3tm1Unc/J mice (an eNOS knockout mouse). Additionally, MK-0626 treatment promoted the mobilization and homing of EPCs to ischemic tissue in eGFP transgenic mouse bone marrow-transplanted ICR mice. We conclude that both the number of circulating EPCs and neo-vasculogenesis are increased in response to DPP-4 inhibitor treatment and that this occurs via an eNOS-dependent mechanism. The results highlight the therapeutic vasculogenesis potential of the DPP-4 inhibitor MK-0626 using a hind limb ischemia mouse model.
    Full-text · Article · Sep 2013 · Current Medicinal Chemistry
  • [Show abstract] [Hide abstract] ABSTRACT: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Its symptoms and signs are varied, and include fever, heart murmur, peripheral embolism, and heart failure. The diagnosis of subacute bacterial endocarditis (SBE) is suggested by a history of an indolent process characterized by fever, fatigue, anorexia, and unexplained weight loss. These patients may have had an invasive procedure, such as dental work, or abused intravenous drugs prior to the diagnosis of SBE. Although uncommon, the patients may present with nonspecific symptoms caused by peripheral embolic events. Herein, we report a 25-year-old male diagnosed with SBE, who presented with the unusual symptom of sudden onset of left upper quadrant abdominal pain for 2 days. His clinical history is also discussed.
    No preview · Article · Jun 2013 · Journal of the Chinese Medical Association
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    [Show abstract] [Hide abstract] ABSTRACT: Herein, we present a case of pneumoaorta and aortoduodenal fistula (ADF) caused by an endoluminal aortic prosthesis infection. An 82-year-old man underwent endovascular aneurysm repair with a stent graft to exclude a 5.1-cm abdominal aortic aneurysm. Three months after the index procedure, the patient was taken to the emergency department at a medical university hospital. He presented with a 2-d history of bloody diarrhea. An endoluminal aortic stent graft infection was diagnosed, and an ADF was identified. The patient died of septic shock despite emergency surgery and intensive care. When encountered, stent graft infections require appropriate antibiotics and graft explantation. The diagnosis of an ADF is important, and surgery remains the most effective management if septic shock presents despite conservative treatment.
    Full-text · Article · Oct 2012 · World Journal of Gastroenterology
  • No preview · Article · Oct 2012 · Journal of Experimental and Clinical Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: [This corrects the article on p. e42808 in vol. 7.].
    Full-text · Article · Aug 2012 · PLoS ONE
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    Dataset: Figure S6
    [Show abstract] [Hide abstract] ABSTRACT: The expression of the 4His-A-AUF1-p37 plasmid, 4His-A-AUF1-p40 plasmid, 4His-A-AUF1-p42 plasmid, and 4His-A-AUF1-p45 plasmid in BAECs. (DOC)
    Full-text · Dataset · Aug 2012
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    Dataset: Figure S3
    [Show abstract] [Hide abstract] ABSTRACT: The sequence of the 3′ and 5′_UTR of the VCAM-1 mRNA. (DOC)
    Full-text · Dataset · Aug 2012
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    Dataset: Figure S4
    [Show abstract] [Hide abstract] ABSTRACT: GroEL1 induces the binding of BAECs/THP-1 cells and impairs the tube formation capacity of the BAECs. (DOC)
    Full-text · Dataset · Aug 2012
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    Dataset: Figure S1
    [Show abstract] [Hide abstract] ABSTRACT: Immunohistochemistry to assess the HuR and TTP expression in the rabbit abdominal aorta. (DOC)
    Full-text · Dataset · Aug 2012
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    Dataset: Figure S2
    [Show abstract] [Hide abstract] ABSTRACT: Fluorescent microscopy and western blot analysis demonstrated that the expression level and distribution of HUR and TTP remained unchanged following GroEL1 treatment. (DOC)
    Full-text · Dataset · Aug 2012
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    Dataset: Figure S5
    [Show abstract] [Hide abstract] ABSTRACT: GroEL1 increases the production of VCAM-1 mRNA and prolongs the stability of the VCAM-1 mRNA in the BAECs. (DOC)
    Full-text · Dataset · Aug 2012
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    [Show abstract] [Hide abstract] ABSTRACT: The expression of vascular adhesion molecule-1 (VCAM-1) by endothelial cells may play a major role in atherogenesis. The actual mechanisms of chlamydia pneumoniae (C. pneumoniae) relate to atherogenesis are unclear. We investigate the influence of VCAM-1 expression in the GroEL1 from C. pneumoniae-administered human coronary artery endothelial cells (HCAECs) and hypercholesterolemic rabbits. In this study, we constructed the recombinant GroEL1 from C. pneumoniae. The HCAECs/THP-1 adhesion assay, tube formation assay, western blotting, enzyme-linked immunosorbent assay, actinomycin D chase experiment, luciferase reporter assay, and immunohistochemical stainings were performed. The results show that GroEL1 increased both VCAM-1 expression and THP-1 cell adhesives, and impaired tube-formation capacity in the HCAECs. GroEL1 significantly increased the VCAM-1 mRNA stability and cytosolic AU-binding factor 1 (AUF1) level. Overexpression of the p37(AUF1) significantly increased VCAM-1 gene expression in GroEL1-induced bovine aortic endothelial cells (BAECs). GroEL1 prolonged the stability of VCAM-1 mRNA by increasing both p37(AUF1) and the regulation of the 5' untranslated region (UTR) of the VCAM-1 mRNA in BAECs. In hypercholesterolemic rabbits, GroEL1 administration enhanced fatty-streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated VCAM-1 expression. In conclusion, GroEL1 induces VCAM-1 expression by p37(AUF1) in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits.
    Full-text · Article · Aug 2012 · PLoS ONE