[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.
PLoS ONE 05/2015; 10(5):e0123971. DOI:10.1371/journal.pone.0123971 · 3.23 Impact Factor
[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.
PLoS ONE 07/2014; 9(7):e102450. DOI:10.1371/journal.pone.0102450 · 3.23 Impact Factor
[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.
CardioRenal Medicine 07/2014; 4(2):130-139. DOI:10.1159/000364835 · 1.89 Impact Factor
[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.
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.
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.
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.
[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.
PLoS ONE 12/2013; 8(12):e84731. DOI:10.1371/journal.pone.0084731 · 3.23 Impact Factor
[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.
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.
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.
FRS could be helpful for physicians in assessing coronary artery disease risk for more targeted therapy among patients with zero to low CAC scores.
Journal of Experimental and Clinical Medicine 12/2013; DOI:10.1016/j.jecm.2013.10.008
[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.
Current Medicinal Chemistry 09/2013; 21(17). DOI:10.2174/09298673113206660273 · 3.85 Impact Factor
[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.
Journal of the Chinese Medical Association 06/2013; DOI:10.1016/j.jcma.2013.05.010 · 0.89 Impact Factor
[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.
World Journal of Gastroenterology 10/2012; 18(37):5309-11. DOI:10.3748/wjg.v18.i37.5309 · 2.43 Impact Factor
[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.
PLoS ONE 08/2012; 7(8):e42808. DOI:10.1371/journal.pone.0042808 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the impact of extracorporeal membrane oxygenation (ECMO) assistance on the clinical outcome of patients with acute myocardial infarction (AMI) that is complicated by profound cardiogenic shock (CS) who received primary percutaneous coronary intervention (PCI).
We collected patients from January 2004 through December 2006 (stage 1); 25 patients who presented with AMI and received primary PCI and had profound CS were enrolled in the study. Intraaortic balloon counterpulsation (IABP) was the only modality for extracorporeal support in our hospital. From January 2007 through December 2009 (stage 2), 33 patients who presented with AMI and received primary PCI and had profound CS were enrolled; for this stage; both intra-aortic balloon counter-pulsation and ECMO support were available in our facility.
A Kaplan-Meier survival analysis displayed significantly improved survival for patients in stage 2 (P = .001; 1-year survival in stage 1 vs 2; 24% vs 63.64%). Patients presenting with either STEMI (ST segment elevation myocardial infarction) or NSTEMI (Non-ST segment elevation myocardial infarction) benefited from ECMO-assisted PCI (P < .05). In stage 1, patients with refractory ventricular tachycardia/ventricular fibrillation had a very low survival rate; however, in stage 2, the survival rate of patients with and without refractory ventricular tachycardia/ventricular fibrillation was similar (P = .316).
Extracorporeal membrane oxygenation-assisted PCI for patients with AMI that is complicated by profound CS may improve the 30-day and 1-year survival rates.
Journal of critical care 05/2012; 27(5):530.e1-530.e11. DOI:10.1016/j.jcrc.2012.02.012 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) plays a major role in oxidized low-density lipoprotein-induced vascular inflammation. Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis, although its specific mechanism remains unknown. This study was conducted to investigate the mechanisms of LOX-1 expression in GroEL1 (a heat shock protein from C. pneumoniae)-administered human coronary artery endothelial cells (HCAECs) and atherogenesis in hypercholesterolemic rabbits. We demonstrated that in the hypercholesterolemic rabbit model, GroEL1 administration enhanced fatty streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated LOX-1 expression. In in vitro study using HCAECs, stimulation with GroEL1 increased TLR4 and LOX-1 expression. Increased LOX-1 expression was downregulated by Akt activation and PI3K-mediated endothelial NO synthase activation. PI3K inhibitor and NO synthase inhibitor induced LOX-1 mRNA production, whereas the NO donor ameliorated the increasing effect of LOX-1 mRNA in GroEL1-stimulated HCAECs. LOX-1 expression was regulated by NADPH oxidase, which mediates reactive oxygen species production and intracellular MAPK signaling pathway in GroEL1-stimulated HCAECs. Treatment with polyethylene-glycol-conjugated superoxide dismutase, apocynin, or diphenylene iodonium significantly decreased GroEL1-induced LOX-1 expression, as did the knockdown of Rac1 gene expression by RNA interference. In conclusion, the GroEL1 protein may induce LOX-1 expression in endothelial cells and atherogenesis in hypercholesterolemic rabbits. The elevated level of LOX-1 in vitro may be mediated by the PI3K-Akt signaling pathway, endothelial NO synthase activation, NADPH oxidase-mediated reactive oxygen species production, and MAPK activation in GroEL1-stimulated HCAECs. The GroEL1 protein of C. pneumoniae may contribute to vascular inflammation and cardiovascular disorders.
The Journal of Immunology 03/2011; 186(7):4405-14. DOI:10.4049/jimmunol.1003116 · 5.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ursolic acid (UA), a triterpenoid compound found in plants, is used in the human diet and in medicinal herbs and possesses a wide range of biological benefits including antioxidative, anti-inflammatory, and anticarcinogenic effects. Endothelial expression of allograft inflammatory factor-1 (AIF-1) mediates vasculogenesis, and nitric oxide (NO) produced by endothelial NO (eNOS) represents a mechanism of vascular protection. It is unclear whether UA affects the neovascularization mediated by AIF-1 and eNOS expression. This study investigated the effects and mechanisms of UA on angiogenesis in vivo in hind limb ischemic animal models and in vitro in human coronary artery endothelial cells (HCECs). This study explored the impact of UA on endothelial cell (EC) activities in vitro in HCECs, vascular neovasculogenesis in vivo in a mouse hind limb ischemia model, and the possible role of AIF-1 in vasculogenesis. The results demonstrate that UA enhances collateral blood flow recovery through induction of neovascularization in a hind limb ischemia mouse model. In vitro data showed that UA increases tube formation and migration capacities in human endothelial cells, and exposing HCECs to UA increased AIF-1 expression through a NO-related mechanism. Moreover, UA administration increased capillary density and eNOS and AIF-1 expression in ischemic muscle. These findings suggest that UA may be a potential therapeutic agent in the induction of neovascularization and provide a novel mechanistic insight into the potential effects of UA on ischemic vascular diseases.
Journal of Agricultural and Food Chemistry 11/2010; 58(24):12941-9. DOI:10.1021/jf103265x · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence and prevalence of peripheral arterial occlusive disease (PAOD) in women is more prevalent than generally appreciated, and the results of surgical treatment are not certain. The purpose of this study was to investigate the result of surgical treatment of PAOD in female patients in our service.
Medical records of female patients undergoing surgical treatment for PAOD in Taipei Veteran General Hospital from January 1, 1997 to July 31, 1998 were reviewed retrospectively. The clinical variables were evaluated, including age, smoking, diabetes mellitus, hypertension, renal function, coexistent coronary disease, history of stroke, Fontaine stages, surgical procedures and results.
There were 20 female patients undergoing surgical treatment for PAOD during the study period, aged from 57 to 91 years, with an average of 73.7 +/- 2.2. Four patients presented with rest pain. Twelve patients presented with gangrene of lower limbs. Ten patients underwent bypass surgery. Three patients received embolectomy. One patient underwent below knee amputation after femoro-popliteal bypass. One patient underwent below knee amputation after embolectomy. Five patients underwent above knee amputation without bypass surgery or embolectomy. Four patients (20%) died after surgery.
The female patients of PAOD presented with severe symptoms and advanced Fontaine stages. The delay in diagnosis and referral resulted in an unsatisfying outcome of surgical treatment. An aggressive approach in diagnosis and referral is necessary for better results.
Journal of the Chinese Medical Association 03/2004; 67(2):79-82. · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relative mortality of coronary artery bypass grafting (CABG) surgery in women is not certain. The purpose of this study was to examine the results of primary, isolated CABG in a series of Taiwanese female patients.
Medical records of 2055 patients (188 women and 1867 men), who underwent primary, isolated CABG at Taipei Veterans General Hospital from January 1, 1991 to December 31, 1999, were reviewed. The mortality rate, associated with clinical and operative variables, was compared between female and male patients.
The female patients had more diabetes (51.6% vs. 29.9%, P<0.01), more hypertension (77.1% vs. 65.0%, P<0.01), and more hypercholesterolemia (39.4% vs. 29.6%, P<0.01), as compared with men. Fewer women consumed cigarette smoking (17.0% vs. 52.1%, P<0.001). Fewer internal mammary artery grafts were used in women (43.1% vs. 57.3%, P<0.001). Nine female (4.8%) and 93 male patients (5.0%) died. There was no significant difference in hospital mortality between women and men. Other variables, including age, angina class, NYHA class, incidence of peripheral arterial occlusive disease, stenosis of left main coronary artery, number of stenotic coronary arteries, incidence of emergent operations, anastomosis number, aortic cross-clamping time, cardiopulmonary bypass time, and left ventricular ejection fraction, were not significantly different between female and male patients.
Although the female patients were more frequently diabetic, hypertensive, and hypercholesterolemic, the hospital mortality of CABG in women was not significantly different from that in men. This result supports an aggressive surgical treatment for women with coronary artery disease.
International Journal of Cardiology 03/2004; 94(1):61-6. DOI:10.1016/j.ijcard.2003.04.010 · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carotid endarterectomy (CEA) is an effective treatment of carotid stenosis to reduce the risk of stroke. The purpose of the current study is to investigate the result of surgical treatment of carotid stenosis in Taipei Veterans General Hospital.
The medical records of 103 patients receiving 113 CEA with or without patch angioplasty in our service between January 1993 and July 1999 were reviewed retrospectively. The clinical and operative variables were collected for analysis. According to the method of carotid arteriotomy closure, all operations were categorized into 3 groups: 76 CEA with venous patch angioplasty, 27 CEA with synthetic angioplasty and 10 primary closure without patch angioplasty. The outcomes of CEA among 3 groups were compared.
There was no significant difference of patient characteristics between 3 groups. Four patients died in the same admission. The incidence of hospital mortality was 0% for venous patch group (p = 0.01), 11.1% for synthetic patch group and 10% for primary closure group. There were 5 perioperative complications including 3 with ipsilateral stroke and 2 with wound hematoma. The incidence of perioperative complication rate was 2.6% for venous patch group, 7.4% for synthetic patch group and 10% for primary closure group (p = 0.87). The incidence of perioperative CVA was 1.3% for venous patch group, 3.7% for synthetic patch group, 10% for primary closure group (p = 0.43).
Our study showed that CEA could be performed with low risk and that venous angioplasty carried lower hospital mortality than other methods of carotid arteriotomy closure.
Zhonghua yi xue za zhi = Chinese medical journal; Free China ed 03/2002; 65(2):69-73.