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Search Results: 1 - 10 of 4330 matches for " Hung-Fat Tse "
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Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease
Carmen Chan, Yok-Lam Kwong, Raymond Y Kwong, Chu-Pak Lau, Hung-Fat Tse
Journal of Cardiovascular Magnetic Resonance , 2010, DOI: 10.1186/1532-429x-12-6
Abstract: We compared the interval changes of left ventricular ejection fraction (LVEF), myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12) injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04) and increase in global LVEF (+9.0%, P = 0.02), the percentage of regional wall thickening (+13.1%, P= 0.04) and MPR (+0.25%, P = 0.03) over the target area at 6-months compared with baseline.Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.Recent clinical studies [1-5] suggest that direct implantation of autologous bone marrow (BM) cells into the ischaemic myocardium improves symptoms and exercise capacity and increases left ventricular (LV) function in patients with severe coronary artery disease (CAD). Despite the absence of trans-differentiation of transplanted BM cells into ischaemic myocardium, improvement in LV function is observed in experimental studies [6,7]. Indeed, emerging evidences from experimental studies indicate than BM cells might exert their benefit via paracrine effects to induce angiogenesis in myocardial ischaemia [6,8,9]. However, there is very limited data on the functional effects of direct BM cells implantation in human [1,2]. Advances in cardiovascular magnetic resonance (CMR) allow non-invasive assessment and serial monitoring of myocardial perfusion by capturing the first-pass perfusion of a bolus of gadolinium injection [10-13]. Furthermore, the use of late gadolinium enhancement (LGE) CMR can identify and q
Characterization of Multiple Ion Channels in Cultured Human Cardiac Fibroblasts
Gui-Rong Li, Hai-Ying Sun, Jing-Bo Chen, Yuan Zhou, Hung-Fat Tse, Chu-Pak Lau
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007307
Abstract: Background Although fibroblast-to-myocyte electrical coupling is experimentally suggested, electrophysiology of cardiac fibroblasts is not as well established as contractile cardiac myocytes. The present study was therefore designed to characterize ion channels in cultured human cardiac fibroblasts. Methods and Findings A whole-cell patch voltage clamp technique and RT-PCR were employed to determine ion channels expression and their molecular identities. We found that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts. These include a big conductance Ca2+-activated K+ current (BKCa) in most (88%) human cardiac fibroblasts, a delayed rectifier K+ current (IKDR) and a transient outward K+ current (Ito) in a small population (15 and 14%, respectively) of cells, an inwardly-rectifying K+ current (IKir) in 24% of cells, and a chloride current (ICl) in 7% of cells under isotonic conditions. In addition, two types of voltage-gated Na+ currents (INa) with distinct properties were present in most (61%) human cardiac fibroblasts. One was a slowly inactivated current with a persistent component, sensitive to tetrodotoxin (TTX) inhibition (INa.TTX, IC50 = 7.8 nM), the other was a rapidly inactivated current, relatively resistant to TTX (INa.TTXR, IC50 = 1.8 μM). RT-PCR revealed the molecular identities (mRNAs) of these ion channels in human cardiac fibroblasts, including KCa.1.1 (responsible for BKCa), Kv1.5, Kv1.6 (responsible for IKDR), Kv4.2, Kv4.3 (responsible for Ito), Kir2.1, Kir2.3 (for IKir), Clnc3 (for ICl), NaV1.2, NaV1.3, NaV1.6, NaV1.7 (for INa.TTX), and NaV1.5 (for INa.TTXR). Conclusions These results provide the first information that multiple ion channels are present in cultured human cardiac fibroblasts, and suggest the potential contribution of these ion channels to fibroblast-myocytes electrical coupling.
Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells
Kwong-Man Ng,Yee-Ki Lee,Wing-Hon Lai,Yau-Chi Chan,Man-Lung Fung,Hung-Fat Tse,Chung-Wah Siu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019787
Abstract: The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway.
Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus
Wen-Sheng Yue, Kui-Kai Lau, Chung-Wah Siu, Mei Wang, Guo-Hui Yan, Kai-Hang Yiu, Hung-Fat Tse
Cardiovascular Diabetology , 2011, DOI: 10.1186/1475-2840-10-113
Abstract: We measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls.Patients with DM had significantly lower circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and higher Log baPWV compared with controls (all P < 0.05). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all P < 0.05). The circulating levels of Log CD34/KDR+ EPC (r = -0.46, P < 0.001) and Log CD133/KDR+ EPC counts (r = -0.45, P < 0.001) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, P < 0.05) and negatively correlated with circulating levels of Log CD34/KDR+ EPC (r = -0.40, P < 0.001) and Log CD133/KDR+ EPC (r = -0.41, P < 0.001). Multivariate analysis revealed that HbA1c, Log CD34/KDR+ and Log CD133/KDR+ EPC counts were independent predictors of Log baPWV (P < 0.05).In patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.It is well recognized that patients with type 2 diabetes mellitus (DM) have accelerated stiffening of the elastic arteries beyond that explained by normal aging [1]. Such increase in arterial stiffness, as measured by pulse wave velocity (PWV) may represent a useful integrated index of vascular status, and has been identified as an independent predictor for cardiovascular related mortality in patients with DM [2]. In patients with DM, one of the postulated mechanisms of increased arterial stiffness is hyperglycemia-induced depletion of endothelial nitric oxide (NO), subsequen
Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with Type 2 Diabetes
Kui-Kai Lau, Yuen-Kwun Wong, Yap-Hang Chan, Kai-Hang Yiu, Kay-Cheong Teo, Leonard Li, Shu-Leong Ho, Koon-Ho Chan, Chung-Wah Siu, Hung-Fat Tse
Cardiovascular Diabetology , 2012, DOI: 10.1186/1475-2840-11-101
Abstract: We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing adverse atherosclerotic events including acute coronary syndrome (ACS) and ischemic stroke [1-3]. Various risk assessment algorithms, for example the Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), aim to predict the likelihood of developing cardiovascular events [4-6]. Some of these scores have also been recalibrated based on the ethnic differences in cardiovascul
Attenuation of Hind-Limb Ischemia in Mice with Endothelial-Like Cells Derived from Different Sources of Human Stem Cells
Wing-Hon Lai, Jenny C. Y. Ho, Yau-Chi Chan, Joyce H. L. Ng, Ka-Wing Au, Lai-Yung Wong, Chung-Wah Siu, Hung-Fat Tse
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057876
Abstract: Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as “off-the-shelf” format for the treatment of tissue ischemia.
An Upregulation in the Expression of Vanilloid Transient Potential Channels 2 Enhances Hypotonicity-Induced Cytosolic Ca2+ Rise in Human Induced Pluripotent Stem Cell Model of Hutchinson Gillford Progeria
Chun-Yin Lo, Yung-Wui Tjong, Jenny Chung-Yee Ho, Chung-Wah Siu, Sin-Ying Cheung, Nelson L. Tang, Shan Yu, Hung-Fat Tse, Xiaoqiang Yao
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087273
Abstract: Hutchinson-Gillford Progeria Syndrome (HGPS) is a fatal genetic disorder characterized by premature aging in multiple organs including the skin, musculoskeletal and cardiovascular systems. It is believed that an increased mechanosensitivity of HGPS cells is a causative factor for vascular cell death and vascular diseases in HGPS patients. However, the exact mechanism is unknown. Transient receptor potential (TRP) channels are cationic channels that can act as cellular sensors for mechanical stimuli. The aim of this present study was to examine the expression and functional role of TRP channels in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from the patients with HGPS. The mRNA and protein expression of TRP channels in HGPS and control (IMR90) iPSC-ECs were examined by semi-quantitative RT-PCRs and immunoblots, respectively. Hypotonicity-induced cytosolic Ca2+ ([Ca2+]i) rise in iPSC-ECs was measured by confocal microscopy. RT-PCRs and immunoblots showed higher expressional levels of TRPV2 in iPSC-ECs from HGPS patients than those from normal individuals. In functional studies, hypotonicity induced a transient [Ca2+]i rise in iPSC-ECs from normal individuals but a sustained [Ca2+]i elevation in iPSC-ECs from HGPS patients. A nonselective TRPV inhibitor, ruthenium red (RuR, 20 μM), and a specific TRPV2 channel inhibitor, tranilast (100 μM), abolished the sustained phase of hypotonicity-induced [Ca2+]i rise in iPSC-ECs from HGPS patients, and also markedly attenuated the transient phase of the [Ca2+]i rise in these cells. Importantly, a short 10 min hypotonicity treatment caused a substantial increase in caspase 8 activity in iPSC-ECs from HGPS patients but not in cells from normal individuals. Tranilast could also inhibit the hypotonicity-induced increase in caspase 8 activity. Taken together, our data suggest that an up-regulation in TRPV2 expression causes a sustained [Ca2+]i elevation in HGPS-iPSC-ECs under hypotonicity, consequently resulting in apoptotic cell death. This mechanism may contribute to the pathogenesis of vascular diseases in HGPS patients.
Stroke Patients with a Past History of Cancer Are at Increased Risk of Recurrent Stroke and Cardiovascular Mortality
Kui-Kai Lau, Yuen-Kwun Wong, Kay-Cheong Teo, Richard Shek-Kwan Chang, Sonny Fong-Kwong Hon, Koon-Ho Chan, Raymond Tak-Fai Cheung, Leonard Sheung-Wai Li, Hung-Fat Tse, Shu-Leong Ho, Chung-Wah Siu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088283
Abstract: Background and Purpose Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke. Methods This was a single center, observational study of 1,105 consecutive Chinese ischemic stroke patients recruited from a large stroke rehabilitation unit based in Hong Kong. We sought to determine whether patients with cancer are at higher risk of recurrent stroke and cardiovascular mortality. Results Amongst 1,105 patients, 58 patients (5.2%) had cancer, of whom 74% were in remission. After a mean follow-up of 76±18 months, 241 patients developed a recurrent stroke: 22 in patients with cancer (38%, annual incidence 13.94%/year), substantially more than those without cancer (21%, 4.65%/year) (p<0.01). In a Cox regression model, cancer, age and atrial fibrillation were the 3 independent predictors of recurrent stroke with a hazard ratio (HR) of 2.42 (95% confidence interval (CI): 1.54–3.80), 1.01 (1.00–1.03) and 1.35 (1.01–1.82) respectively. Likewise, patients with cancer had a higher cardiovascular mortality compared with those without cancer (4.30%/year vs. 2.35%/year, p = 0.08). In Cox regression analysis, cancer (HR: 2.08, 95% CI: 1.08–4.02), age (HR: 1.04, 95% CI 1.02–1.06), heart failure (HR: 3.06, 95% CI 1.72–5.47) and significant carotid atherosclerosis (HR: 1.55, 95% CI 1.02–2.36) were independent predictors for cardiovascular mortality. Conclusions Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.
Long-term oral nitrate therapy is associated with adverse outcome in diabetic patients following elective percutaneous coronary intervention
Kai Hang Yiu, Vincent Pong, Chung Wah Siu, Chu Pak Lau, Hung Fat Tse
Cardiovascular Diabetology , 2011, DOI: 10.1186/1475-2840-10-52
Abstract: The incidence of major adverse cardiovascular events (MACEs) following elective PCI for stable coronary artery disease was evaluated in 108 patients with type II diabetes (age 64.6 ± 10.5 years, 67.7% men). Major adverse cardiovascular events were defined as the need for revascularization, non-fatal myocardial infarction or cardiovascular death. Multivariate Cox regression analysis was used to evaluate the predictive value of MACEs by clinical characteristics and the prescription of long-term nitrate therapy.Isosorbide mononitrate (ISMN) was prescribed to 46 patients with an average dose of 44.3 ± 15.2 mg/day. After a mean follow up of 25.3 ± 25 months, 16 patients developed MACEs. Patients who received ISMN were more likely to suffer from MACEs (26.1% vs. 6.5%, P = 0.01), mainly driven by a higher rate of acute coronary syndrome (13.0 vs 0%, P = 0.01). Average daily dose of nitrate and other cardiovascular medication was not associated with MACEs. Multivariate Cox regression analysis revealed that prescription of only ISMN (Hazard Ratio 3.09, 95% CI 1.10-10.21, P = 0.04) was an independent predictor for the development of MACEs.Long-term oral nitrate therapy was associated with MACEs following elective coronary artery revascularization by PCI in patients with type II diabetes.Elective percutaneous coronary intervention (PCI) is a common treatment for patients with stable coronary artery disease and comprises 85% of all PCI procedures [1,2]. Diabetic patients account for up to one quarter of patients who undergo PCI each year and experience a higher rate of post-operative adverse cardiovascular events than non-diabetics [3].Organic nitrate remains one of the most frequently prescribed anti-anginal agents for the treatment of coronary artery disease (CAD), although no long-term beneficial effect has been proven [4]. Previous clinical trials have suggested that continuous administration of oral nitrates paradoxically increases adverse cardiac events following myocardi
An Observational, Prospective Survey Assessing the Control of Atrial Fibrillation in Asia Pacific: Rationale and Design of the RecordAF-AP Registry
John Amerena, Shih-Ann Chen, Charn Sriratanasathavorn, Jeong-Gwan Cho, Huang Dejia, Razali Omar, Tse Hung Fat and Anthony King
Clinical Medicine Insights: Cardiology , 2012, DOI: 10.4137/CMC.S6289
Abstract: Background: The literature suggests that the prevalence of atrial fibrillation (AF) may be lower in Asian countries than in Western countries. Nevertheless, AF remains a significant public health problem in the region. The burden of AF, the experiences of previous trials and the lack of data on AF and its management in Asia Pacific highlight the need for a comprehensive prospective study of AF management. Methods: The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation Asia Pacific (RecordAF-AP) is a prospective, observational survey of the management of recently diagnosed AF patients with 1-year follow-up in 8 countries across Asia Pacific. Eligible patients presenting with AF, treated or not, will be included in the registry and data will be recorded prospectively during follow-up visits at 6 and 12 months. Results: RecordAF-AP will recruit more than 3000 patients. Study recruitment commenced in April 2009 and the final results anticipated at the end of 2011. Conclusions: RecordAF-AP will assess the real-life management of AF patients in Asia Pacific, including a comparison of clinical outcomes in rhythm versus rate control strategies, providing much needed insight into the costs, treatment choices and clinical outcomes of AF patients in this region.
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