Hon-Kan Yip

Chang Gung University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (233)615.32 Total impact

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    ABSTRACT: Aim: Cardiac and renal diseases are common disorders that frequently coexist. We tested the hypothesis that the levels of circulating endothelial-derived apoptotic microparticles (EDA-MPs; CD31(+)CD42b(-)AN(-)V(+)) and platelet-derived apoptotic microparticles (PDA-MPs; CD31(+)CD42b(+)AN(-)V(+)) are useful biomarkers for predicting the presence of cardiorenal disease (CRD). Methods: A total of 68 patients with chronic kidney disease (CKD) and angina pectoris (CKD-AP) undergoing cardiac catheterization were prospectively enrolled into group 1, 10 patients with coronary artery disease (CAD) without CKD were enrolled into group 2 (CAD(+)CKD(-)) and 10 patients without CAD and CKD were enrolled into group 3 (CAD(-)CKD(-)). Results: The serum creatinine levels were significantly higher, whereas the estimated glomerular filtration rates (eGFRs) were significantly lower, in group 1 than in the other two groups (all p<0.02). The circulating levels of EDA-MPs and PDA-MPs did not differ between the patients with and without CKD (all p>0.2). However, the circulating levels of EDA-MPs and PDA-MPs were significantly higher in group 2 than in groups 1 and 3 (all p<0.03). In addition, differences were noted in the circulating EDA-MP and PDA-MP levels between groups 1 and 3, although without statistical significance (all p>0.09). Meanwhile, among the CKD patients, the subgroup analysis showed that the levels of MPs were significantly higher in those with CAD than in those without (all p=0.001), while a multivariate analysis demonstrated that CAD was the only factor independently predictive of high levels of circulating EDA-MPs and PDA-MPs (p=0.033). Conclusions: The link with increased circulating levels of MPs is more consistent in patients with CAD than in those with CKD.
    Journal of atherosclerosis and thrombosis. 10/2014;
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    ABSTRACT: Background Ad hoc percutaneous coronary intervention (PCI) which performed immediately after diagnostic catheterization has become the most common way of coronary intervention. However, limited data is available on in-hospital and long-term outcome comparing ad hoc and staged chronic total occlusion (CTO) PCI. Our aim of the study was to figure the short-term and long-term outcome after ad hoc or staged CTO PCI. Methods This retrospective analysis included consecutive 512 patients underwent 561 CTO PCI procedures between January 2002 and December 2009. Patient basic demographics, lesion characteristics, interventional procedure, devices used and in-hospital outcomes were compared between ad hoc and staged CTO PCI groups. 3-year clinical outcomes included all-cause mortality, cardiac mortality, myocardial infarction (MI), the need for coronary artery bypass graft surgery (CABG), major adverse cardiac events (MACE) and target vessel revascularization (TVR) were compared. Time-to-event analyses were performed using Kaplan-Meier statistics. Results Four hundred and fifty-one patients (80.4%) were enrolled in ad hoc CTO PCI group. Final successful revascularization was higher in ad hoc CTO PCI group compared with staged CTO PCI group (82.9 vs. 77.3%, p = 0.17) without statistical significance. There was no significant difference between ad hoc CTO PCI and staged CTO PCI groups in in-hospital outcomes such as all-cause mortality, cardiac death, myocardial infarction, urgent bypass surgery, urgent PCI or complications. Patients with ad hoc CTO PCI had lower rate of all-cause mortality (6.2% vs. 6.5%, p = 0.89), the need for CABG (1.9% vs. 2.1%, p = 0.89) but higher rate of cardiac mortality (1.7% vs. 0.0%, p = 0.21), MI (1.0% vs. 0.0%, p = 0.34), MACE (24.1% vs. 17.5%, p = 0.19) and TVR (17.8% vs. 10.0%, p = 0.069) without statistical significance in 3-year clinical outcomes. Conclusion 3-year clinical outcomes compared with ad hoc CTO PCI and staged CTO PCI had insignificant differences between: all-cause mortality, cardiac mortality, MI, the need for CABG, MACE and TVR.
    IJC Heart & Vessels. 07/2014;
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    ABSTRACT: Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.
    International Heart Journal 06/2014; · 1.23 Impact Factor
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    ABSTRACT: We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA). A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p < 0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p < 0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p < 0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.
    Journal of Translational Medicine 04/2014; 12(1):101. · 3.46 Impact Factor
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    ABSTRACT: We tested the hypothesis that, as compared with conventional door-to-balloon, shortened door-to-balloon time would further improve 30-day outcome in ST-elevation myocardial infarction (STEMI) patients undergoing primary stenting. Retrospective cohort study SETTING:: Academic tertiary care hospital with approximately 2600 beds PATIENTS:: Between January 2008 and December 2009, 266 ST-elevation myocardial infarction patients underwent primary stenting with conventional Door-to-baloon were consecutively enrolled as group 1, while 293 ST-elevation myocardial infarction patients underwent primary stenting with shortened door-to-balloon between January 2010 and December 2011 were consecutively enrolled as group 2. Shorten door-to-balloon time. The results showed that time from chest pain onset to door did not differ between two groups (p > 0.1), whereas door-to-balloon time was significantly reduced in group 2 compared with that in group 1 (p < 0.0001). The prevalences of successful reperfusion, acute and subacute stent thrombosis, 30-day death or combined endpoint (defined as congestive heart failure ≥ New York Heart Association functional class 3 or 30-d death), and left ventricular function did not differ between two groups (all p > 0.05), whereas the peak creatine phosphokinase level was significantly reduced in group 2 (< 0.05). Further analysis showed that shortening the chest pain-to-reperfusion time to less than 240 minutes was the most important factor in improving left ventricular function (p < 0.001) and 30-day combined endpoint. Multivariate analysis showed that congestive heart failure greater than or equal to New York Heart Association functional class 3, poor left ventricular function, and age (all p < 0.001) along with unsuccessful reperfusion (p = 0.25) were independently predictive of 30-day mortality. Shortening the duration between chest pain onset and reperfusion to less than 4.0 hours was critical in reducing myocardial necrosis and improving heart function and 30-day mortality.
    Critical care medicine 04/2014; · 6.37 Impact Factor
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    ABSTRACT: This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.
    International journal of cardiology 03/2014; · 6.18 Impact Factor
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    ABSTRACT: Aims: Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in patients undergoing percutaneous coronary intervention (PCI). Limited data, however, are available on predictors of CIN in PCI for chronic total occlusion (CTO) lesions. The aim of the study was to determine the risk of developing CIN in patients undergoing CTO PCI by studying the effects of clinical variables, interventional techniques, and CTO lesion characteristics on renal function. Methods and results: This retrospective analysis included consecutive patients referred for CTO PCI between January 2002 and December 2009. CIN was defined as an elevated serum creatinine level ≥25% of baseline serum creatinine level at 48-72 hours after procedure. Patient characteristics, Mehran score, lesion characteristics, interventional procedure, and devices used were compared between CIN and non-CIN groups. For the 516 patients eligible for analysis, the incidence of CIN was 5.4% (28/516). Two patients needed transient haemodialysis (0.4%, 2/516). Analysis of risk using Mehran scoring found that the incidence of CIN was 0.5% (1/207) among low-risk patients, 3.4% (7/205) among moderate-risk patients, 15.9% (14/88) among high-risk patients and 37.5% (6/16) among very high-risk patients. The Mehran score high-risk group (11-15) and the very high-risk group (≥16) were definitely predictors of CIN after CTO PCI (OR: 27.022 [95% CI: 2.787-262.028, p=0.004]; OR: 32.512 [95% CI: 2.149-491.978, p=0.012]). Severe tortuosity was the only predictor of CIN after CTO PCI in angiographic and procedural findings (OR: 6.621 [95% CI: 1.090-40.227, p=0.040]). Conclusions: Being in the Mehran score high-risk group (11-15) or the very high-risk group (≥16) and severe tortuosity were predictors of CIN after CTO PCI.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 02/2014; 9(10):1173-80. · 3.17 Impact Factor
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    ABSTRACT: Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke.
    BioMed research international. 01/2014; 2014:214587.
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    ABSTRACT: This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury.
    American Journal of Translational Research 01/2014; 6(5):439-58.
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    ABSTRACT: Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC). Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n = 56) (one-year survivors) and patients who survived less than one year were categorized into group 2 (n = 51) (one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P < 0.05). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P = 0.006). Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P < 0.035). Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.
    BioMed Research International 01/2014; 2014:173401. · 2.71 Impact Factor
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    ABSTRACT: This study investigates the therapeutic potential of intracoronary tacrolimus against acute myocardial infarction (AMI) in minipigs with serial cardiac magnetic resonance (CMR) and changes at histological and protein levels. Twelve minipigs subjected to permanent left anterior descending artery ligation were randomized as tac-treated group (n = 6, with intracoronary tacrolimus treatment) and controls (n = 6). CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative days 2, 5, and 21. There were no significant differences in left ventricular function (LVF), contractility, and LGE between the two groups on day 2. On day 5, the tac-treated group showed a significantly higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio than controls. On day 21, the controls demonstrated further deterioration of LVF and infarct. Contrastingly, the tac-treated animals demonstrated preservation of LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct ratios compared with those on day 5 and controls. The in vivo CMR results were correlated with in vitro findings on histology, immunostaining, and Western blotting which revealed significantly less fibrosis, higher vascularities, less CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF-κB, and TNF-α), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls.
    BioMed Research International 01/2014; 2014:524078. · 2.71 Impact Factor
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    ABSTRACT: This study evaluated the feasibility, safety, and prognostic outcome in patients with significant unprotected left main coronary artery (ULMCA) disease undergoing stenting.
    PLoS ONE 01/2014; 9(10):e109281. · 3.53 Impact Factor
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    ABSTRACT: We tested the hypothesis that apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) are superior to healthy (H)-ADMSC in attenuating cecal ligation puncture (CLP)-induced sepsis-mediated lung and kidney injuries. Adult male rats divided into group 1 (sham controls), group 2 (CLP), group 3 [CLP + H-ADMSC administered at 0.5, 6, and 18 hours after CLP], and group 4 [CLP + A-ADMSC administered as in group 3] were sacrificed 72 hours after CLP with blood, lung, and kidney collected for studies. White blood cell (WBC) count, circulating TNF-α and creatinine levels were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Kidney and lung damage scores were highest in group 2, lowest in group 1, significantly higher in group 3 than in group 4 (all P < 0.0001). Protein expressions of inflammatory (ICAM-1, MMP-9, TNF-α, NF-κB), oxidative, and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than groups 1 and 4, whereas anti-apoptotic (Bcl-2) and mitochondrial integrity (cytochrome-C) biomarkers were lower in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Expressions of anti-oxidant biomarkers at protein (GR, GPx, NQO-1, HO-1) and cellular (GR, GPx) levels were highest in group 4 (all P < 0.001). The number of inflammatory cells (CD3+) in lungs and levels of DNA damage marker (γ-H2AX) in kidneys were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). A-ADMSC therapy was superior to H-ADMSC therapy in protecting major organs from damage in rats with CLP-induced sepsis syndrome.
    Stem Cell Research & Therapy 12/2013; 4(6):155. · 3.65 Impact Factor
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    ABSTRACT: Idiopathic azygos vein aneurysm (AVA) is rare. This retrospective study evaluated the imaging features and outcomes in 10 cases of idiopathic AVA. We retrospectively evaluated 10 patients with surgically proven or typical imaging features of idiopathic AVA encountered in our institution between 1990 and 2012. Chest roentgenography and computed tomography (CT) were performed in all 10 patients, and magnetic resonance imaging (MRI) was performed in 4 of these patients. The clinical features, AVA morphologic characteristics, and outcomes were analyzed. Chest roentgenograms showed a right paratracheal nodule or mediastinal mass in 7 cases. CT and MRI disclosed 4 thrombosed saccular AVAs (short axis, 3-6 cm; mean, 4.7 cm) and 6 fusiform AVAs (short axis, 2.2-3 cm; mean 2.7 cm). Two large saccular AVAs that presented with chest tightness were resected shortly after diagnosis. One saccular AVA manifested as a pulmonary embolism, whereas the remaining AVA was asymptomatic; they showed 25% to 40% short-axis growth in a 3- to 5-year interval before subsequent AVA resection. Conversely, all 6 fusiform AVAs were asymptomatic and found incidentally, remaining rather stable with less than 8% short-axis growth during 3 to 8 years of follow-up. Compared with fusiform AVAs, saccular AVAs were larger and had a greater frequency of AVA-related symptoms, intralesional thromboses, and greater than 20% short-axis growth during the follow-up period. Saccular AVAs are larger than fusiform aneurysms, presenting with greater frequency of chest symptoms, intralesional thrombosis, considerable lesion growth, and need for surgical intervention. In contrast, fusiform AVAs are asymptomatic and rather stable in long-term follow-up.
    The Annals of thoracic surgery 12/2013; · 3.45 Impact Factor
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    ABSTRACT: This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery. Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0mg/kg)] and group 4A [CLI-tPA (intravenously at 3h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0mg/kg)], and group 4B (CLI-tPA). The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p<0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p>0.05) at 6h and 18h post-CLI. Levels of these biomarkers decreased again 14days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p<0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p<0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p<0.01). tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.
    International journal of cardiology 11/2013; · 6.18 Impact Factor
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    ABSTRACT: This study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals. By post-AMI day 21, left ventricular ejection fraction (LVEF) was lowest in untreated AMI animals, significantly higher in SC than in AMI-Tac group (all p<0.003). Infarct areas at basal, middle, and apical levels, numbers of CD14+ and iNOS+ cells in infarct area (IA) and peri-IA, and protein expression of CD14, CD68, and Ly6g from circulating inflammatory cells showed an opposite pattern compared with that of LVEF in all groups (all p<0.005). Protein expressions of MCP-1, MIP-1, TNF-alpha, NF-kappaB, iNOS, and IL-12 in IA and peri-IA exhibited an identical pattern compared to that of CD14, CD68, and Ly6g from circulating inflammatory cells (all p<0.01). Expressions of myocardial damage biomarkers in IA and peri-IA [gamma-H2AX, beta-myosin heavy chain (MHC), Smad3, TGF-beta] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, alpha-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001). Innate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment.
    Journal of Biomedical Science 10/2013; 20(1):82. · 2.46 Impact Factor
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    ABSTRACT: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury. Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 mum/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2--4). Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-alpha, IL-1beta, PAI-1), protein (TNF-alpha, NF-kappaB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (gammaH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01). Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
    Journal of Translational Medicine 10/2013; 11(1):270. · 3.46 Impact Factor
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    ABSTRACT: Aims: The association between an elevated serum neopterin level and the development of coronary artery complex lesions has been extensively assessed; however, the correlation between the serum neopterin level and the development of carotid artery stenosis has seldom been reported. This study tested whether this biomarker is increased in patients with severe carotid artery stenosis (≥70%) undergoing carotid artery (CA) stenting and investigated independent predictors of an increased circulating neopterin level.Methods: Fifty patients with severe CA stenosis (CAS) undergoing CA stenting were consecutively enrolled in this study from January 2009 through December 2011. The serum neopterin levels of age- and gender-matched acute ischemic stroke (AIS) patients (n=120) and control subjects (CS) (n=33) were also measured. A blood sample was prospectively collected from each patient in the catheterization room.Results: The serum levels of neopterin were significantly higher in the CAS patients than in the AIS patients or CS and significantly higher in the AIS patients than in the CS (all p<0.001). An analysis of the variables of 170 patients (CAS+AIS) demonstrated that age, a previous history of stroke and severe CAS were significantly correlated with an increased serum level of neopterin (all p<0.005). A multivariate binary logistic regression analysis of the severe CAS patients (n=50) demonstrated that age and the creatinine level were independent predictors of a high neopterin level (neopterin level ≥16.52 ng/dL, i.e., according to the median value of neopterin) (all p<0.05).Conclusions: The circulating neopterin levels are significantly higher in patients with severe CAS than in those with AIS. The presence of CAS, age and the creatinine level were significantly correlated with an increased serum neopterin level.
    Journal of atherosclerosis and thrombosis 09/2013; · 2.93 Impact Factor
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    ABSTRACT: This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p<0.001). Pulmonary damage severity (thickened alveolar septum and pulmonary arteriolar wall, decreased alveolar-sac numbers), number of CD3+ cells, and protein expressions of inflammatory (MMP-9, NF-κB, VCAM-1, angiotensin II-receptor), apoptotic (Bax, caspase 3, cleaved PARP), and fibrotic (TGF-β, Smad3) biomarkers showed an identical pattern compared to that of RVSBP, whereas pulmonary expressions of anti-apoptotic (Bcl-2) and anti-fibrotic (BMP-2, Smad1/5) biomarkers displayed a reverse pattern (all p<0.01). The protein expressions of RV damage markers (BNP, caspase 3) were increased, whereas expression of biomarker for RV functional preservation (Cx43) was reduced in group 2 compared with group 1, elevated in groups 3 and 4 compared to group 2, and further increased in group 5 (all p<0.01). Combined therapy with nicorandil and colchicine is superior to either alone in attenuating MCT-induced PAH in rats.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2013; · 2.61 Impact Factor
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    ABSTRACT: We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis. Adipose tissue from adult-male Fischer 344 rats (n = 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n = 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4). In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c-kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P < 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P < 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor + cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P < 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P < 0.01). Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.
    Cytotherapy 07/2013; · 3.06 Impact Factor

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2k Citations
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Institutions

  • 2008–2014
    • Chang Gung University
      • • Department of Cardiology
      • • Department of Internal Medicine
      • • College of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2001–2014
    • Chang Gung Memorial Hospital
      • • Division of Cardiology
      • • Division of General Surgery
      • • Division of Neurosurgery
      T’ai-pei, Taipei, Taiwan
  • 2010–2013
    • National Pingtung University of Science and Technology
      • Department of Life Science
      P’ing-tung-chieh, Taiwan, Taiwan
  • 2007–2013
    • I-Shou University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2010–2011
    • National Dong Hwa University
      • Department of Electrical Engineering
      Hualian, Taiwan, Taiwan
  • 2007–2010
    • Suez Canal University
      • Department of Cardiology
      Ismailia, Muhafazat al Isma`iliyah, Egypt
  • 2004–2010
    • National Sun Yat-sen University
      • Department of Biological Science
      Kaohsiung, Kaohsiung, Taiwan
  • 2009
    • Kaohsiung Medical University
      • College of Medicine
      Kaohsiung, Kaohsiung, Taiwan