33 results on '"Sarah, Chua"'
Search Results
2. Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress
- Author
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Tzu-Hsien Tsai, Cheng-Jei Lin, Sarah Chua, Sheng-Ying Chung, Shyh-Ming Chen, Chien-Ho Lee, and Chi-Ling Hang
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diabetic cardiomyopathy ,RasgRF1 ,heart failure ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1−/−) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1−/− mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1−/− mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1−/− mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1−/− mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.
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- 2018
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3. Combined Therapy with SS31 and Mitochondria Mitigates Myocardial Ischemia-Reperfusion Injury in Rats
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Fan-Yen Lee, Pei-Lin Shao, Christopher Glenn Wallace, Sarah Chua, Pei-Hsun Sung, Sheung-Fat Ko, Han-Tan Chai, Sheng-Ying Chung, Kuan-Hung Chen, Hung-I Lu, Yi-Ling Chen, Tien-Hung Huang, Jiunn-Jye Sheu, and Hon-Kan Yip
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ischemia-reperfusion ,oxidative stress ,mitochondria ,SS31 ,left ventricular ejection fraction ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at 30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR-SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative-stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3 expression and ATP levels. In adult male rats 72 h after IR, left ventricular ejection fraction (LVEF) was highest in sham-operated control animals and lowest in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than untreated IR rats or those treated with Mito or SS31 alone. Areas of fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers (MMP-9, CD11, IL-1β, TNF-α), apoptotic markers (mitochondrial-Bax, cleaved-caspase-3, PARP), fibrosis markers (p-Smad3, TGF-β), DNA-damage (γ-H2AX), sarcomere-length, and pressure/volume overload markers (BNP, β-MHC) all showed a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and energy integrity (PGC-1α/mitochondrial cytochrome-C) markers exhibited a pattern identical to that of LVEF. This study demonstrates that the combined SS31-Mito therapy is superior to either therapy alone for protecting myocardium from IR injury and indicates that the responsible mechanisms involved increased SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and protects mitochondrial integrity.
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- 2018
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4. Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model
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Cheuk-Kwan Sun, Yen-Yi Zhen, Hung-I Lu, Pei-Hsun Sung, Li-Teh Chang, Tzu-Hsien Tsai, Jiunn-Jye Sheu, Yung-Lung Chen, Sarah Chua, Hsueh-Wen Chang, Yi-Ling Chen, Fan-Yen Lee, and Hon-Kan Yip
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Internal medicine ,RC31-1245 - Abstract
We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.
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- 2014
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5. Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment.
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Morgan Fu, Cheuk-Kwan Sun, Yu-Chun Lin, Ching-Jen Wang, Chiung-Jen Wu, Sheung-Fat Ko, Sarah Chua, Jiunn-Jye Sheu, Chiang-Hua Chiang, Pei-Lin Shao, Steve Leu, and Hon-Kan Yip
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Medicine ,Science - Abstract
An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy may be a therapeutic alternative under such clinical situation. Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD). Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only) and group 2 (Constrictor over LAD plus ECSW [800 impulses at 0.09 mJ/mm(2)] once 3 months after the procedure). Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV) angiography showed higher LV ejection fraction and lower LV end-systolic dimension and volume in group 2 on day 180 (p
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- 2011
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6. Diabetes Mellitus: An Independent Risk Factor of In-Hospital Mortality in Patients with Infective Endocarditis in a New Era of Clinical Practice
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Chi-Ling Hang, Sheng-Ying Chung, Cheng-Jei Lin, Sarah Chua, and Tzu-Hsien Tsai
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Adult ,Male ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,macromolecular substances ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Risk of mortality ,Medicine ,Humans ,030212 general & internal medicine ,Hospital Mortality ,Risk factor ,Aged ,Creatinine ,Endocarditis ,business.industry ,infective endocarditis ,Incidence (epidemiology) ,Mortality rate ,musculoskeletal, neural, and ocular physiology ,Incidence ,lcsh:R ,Public Health, Environmental and Occupational Health ,Middle Aged ,Staphylococcal Infections ,medicine.disease ,Prognosis ,mortality ,chemistry ,nervous system ,Infective endocarditis ,diabetes mellitus ,Observational study ,Female ,business - Abstract
Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17&ndash, 25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p <, 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p <, 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p <, 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.
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- 2019
7. Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress
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Sarah Chua, Chien-Ho Lee, Shyh-Ming Chen, Chi-Ling Hang, Tzu-Hsien Tsai, Cheng-Jei Lin, and Sheng-Ying Chung
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0301 basic medicine ,Diabetic Cardiomyopathies ,Cardiac fibrosis ,heart failure ,RasgRF1 ,030204 cardiovascular system & hematology ,medicine.disease_cause ,lcsh:Chemistry ,Mice ,0302 clinical medicine ,Diabetic cardiomyopathy ,diabetic cardiomyopathy ,Myofibroblasts ,lcsh:QH301-705.5 ,Spectroscopy ,Mice, Knockout ,General Medicine ,Extracellular Matrix ,Computer Science Applications ,cardiovascular system ,Cytokines ,Inflammation Mediators ,medicine.symptom ,medicine.drug ,Cardiac function curve ,medicine.medical_specialty ,Inflammation ,Streptozocin ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,ras-GRF1 ,business.industry ,Organic Chemistry ,Streptozotocin ,medicine.disease ,Fibrosis ,Disease Models, Animal ,Oxidative Stress ,Glucose ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,lcsh:Biology (General) ,lcsh:QD1-999 ,Heart failure ,Myocardial fibrosis ,business ,Biomarkers ,Gene Deletion ,Oxidative stress - Abstract
Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1&minus, /&minus, ) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1&minus, mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1&minus, mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1&minus, mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1&minus, mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.
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- 2018
- Full Text
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8. An Unusual Adult Complex Congenital Heart Disease
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Wei-Chieh Lee, Yi Wei Lee, and Sarah Chua
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03 medical and health sciences ,Pediatrics ,medicine.medical_specialty ,0302 clinical medicine ,Text mining ,business.industry ,General Engineering ,medicine ,030212 general & internal medicine ,Images in Clinical Medicine ,030204 cardiovascular system & hematology ,Complex congenital heart disease ,business - Published
- 2018
9. Biomarkers Associated with Vascular and Valvular Calcification in Chronic Hemodialysis Patients
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Chien-Te Lee, Sarah Chua, Chung-Yao Hsu, Yu-Che Tsai, Hwee-Yeong Ng, Chien-Chun Kuo, Chien-Hsing Wu, Te-Chun Chen, Terry Ting-Yu Chiu, and Yueh-Ting Lee
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Male ,lcsh:R5-920 ,hemodialysis ,Biochemistry (medical) ,Clinical Biochemistry ,Calcinosis ,General Medicine ,Middle Aged ,Logistic Models ,Renal Dialysis ,valvular calcification ,Genetics ,biomarker ,Blood Vessels ,Humans ,Female ,Other ,lcsh:Medicine (General) ,Molecular Biology ,Biomarkers ,Vascular calcification ,Aged - Abstract
Background: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients.Methods: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared.Results: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC.Conclusions: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.
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- 2013
10. Comparison of acute versus convalescent stage high-sensitivity C-Reactive protein level in predicting clinical outcome after acute ischemic stroke and impact of erythropoietin
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Sheng-Ying Chung, Steve Leu, Hung-Sheng Lin, Tzu-Hsien Tsai, Chun-Man Yuen, Han-Tan Chai, Hon-Kan Yip, Yung-Lung Chen, Kuo-Ho Yeh, and Sarah Chua
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Male ,medicine.medical_specialty ,acute ischemic stroke ,media_common.quotation_subject ,lcsh:Medicine ,Placebo ,Gastroenterology ,Statistics, Nonparametric ,General Biochemistry, Genetics and Molecular Biology ,Brain Ischemia ,law.invention ,Brain ischemia ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Stroke ,Aged ,media_common ,Medicine(all) ,biology ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Convalescence ,C-reactive protein ,lcsh:R ,Case-control study ,General Medicine ,Middle Aged ,medicine.disease ,adverse clinical outcome ,C-Reactive Protein ,Logistic Models ,Treatment Outcome ,ROC Curve ,Erythropoietin ,Case-Control Studies ,Multivariate Analysis ,biology.protein ,Female ,high-sensitivity C-reactive protein ,erythropoietin ,business ,medicine.drug - Abstract
Background and Aim Currently, no data on the optimal time point after acute ischemic stroke (IS) at which high-sensitivity C-reactive protein (hs-CRP) level is most predictive of unfavorable outcome. We tested the hypothesis that hs-CRP levels during both acute (48 h after IS) and convalescent (21 days after IS) phases are equally important in predicting 90-day clinical outcome after acute IS. We further evaluated the impact of erythropoietin (EPO), an anti-inflammatory agent, on level of hs-CRP after acute IS. Methods Totally 160 patients were prospectively randomized to receive either EPO therapy (group 1, n = 80) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or placebo (group 2, n = 80). Serum level of hs-CRP was determined using ELISA at 48 h and on day 21 after IS and once in 60 healthy volunteers. Results Serum level of hs-CRP was substantially higher in all patients with IS than in healthy controls at 48 h and day 21 after IS (all p < 0.001). Levels of hs-CRP did not differ between group 1 and 2 at 48 h and day 21 after IS (all p > 0.5). Multivariate analysis showed that hs-CRP levels (at 48 h and day 21) were independently predictive of 90-day major adverse neurological event (MANE) (defined as recurrent stroke, NIHSS≥8, or death) (all p < 0.03), whereas EPO therapy was independently predictive of reduced 90-day MANE (all p < 0.02). Conclusion EPO therapy which was independently predictive of freedom from 90-day MANE did not alter the crucial role of hs-CRP levels measured at 48 h and 21-day in predicting unfavorable clinical outcome after IS.
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- 2012
11. Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke
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Tzu-Hsien Tsai, Yu-Chun Lin, Hon-Kan Yip, Ying-Hsien Kao, Steve Leu, Pei-Lin Shao, Yung-Lung Chen, Cheuk-Kwan Sun, Chia-Hung Yen, Chun-Man Yuen, Sarah Chua, and Li-Teh Chang
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Male ,Pathology ,lcsh:Medicine ,Apoptosis ,medicine.disease_cause ,Rats, Sprague-Dawley ,Stroke ,Medicine(all) ,Glial fibrillary acidic protein ,biology ,Cytochromes c ,RNA-Binding Proteins ,General Medicine ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Aquaporin 4 ,Brain infarction ,Cyclosporine ,Cardiology ,Drug Therapy, Combination ,medicine.symptom ,medicine.drug ,Brain Infarction ,medicine.medical_specialty ,Inflammation ,General Biochemistry, Genetics and Molecular Biology ,Pharmacotherapy ,Internal medicine ,Glial Fibrillary Acidic Protein ,In Situ Nick-End Labeling ,medicine ,Animals ,RNA, Messenger ,Erythropoietin ,Cell Nucleus ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,lcsh:R ,Recovery of Function ,medicine.disease ,Rats ,Oxidative Stress ,Gene Expression Regulation ,biology.protein ,business ,Oxidative stress ,Transcription Factors - Abstract
Background This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS). Methods Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery. Results BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01). Conclusion combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS.
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- 2011
12. Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment
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Ching-Jen Wang, Steve Leu, Morgan Fu, Cheuk-Kwan Sun, Chiang-Hua Chiang, Yu-Chun Lin, Sheung-Fat Ko, Hon-Kan Yip, Chiung-Jen Wu, Pei-Lin Shao, Jiunn-Jye Sheu, and Sarah Chua
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Male ,Pathology ,Swine ,Myocardial Infarction ,lcsh:Medicine ,Coronary Artery Disease ,medicine.disease_cause ,Cardiovascular ,Ventricular Dysfunction, Left ,Enos ,Fibrosis ,Medicine ,lcsh:Science ,Multidisciplinary ,Ejection fraction ,biology ,Ventricular Remodeling ,Animal Models ,medicine.anatomical_structure ,Echocardiography ,Cardiology ,Swine, Miniature ,medicine.symptom ,Immunohistochemical Analysis ,Artery ,Research Article ,medicine.medical_specialty ,Clinical Research Design ,Immunology ,Ischemia ,Inflammation ,Microbiology ,High-Energy Shock Waves ,Model Organisms ,Internal medicine ,Animals ,Animal Models of Disease ,Ventricular remodeling ,Biology ,Heart Failure ,business.industry ,Acute Cardiovascular Problems ,lcsh:R ,Immunity ,biology.organism_classification ,medicine.disease ,Immunologic Techniques ,Clinical Immunology ,lcsh:Q ,business ,Oxidative stress - Abstract
An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy may be a therapeutic alternative under such clinical situation. Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD). Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only) and group 2 (Constrictor over LAD plus ECSW [800 impulses at 0.09 mJ/mm(2)] once 3 months after the procedure). Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV) angiography showed higher LV ejection fraction and lower LV end-systolic dimension and volume in group 2 on day 180 (p
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- 2011
13. Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views
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Jennifer H. Neary, Robert A. Levine, Morgan Fu, Mark D. Handschumacher, Judy Hung, Thanh-Thao Ton-Nu, John Chu, Chiung Jen Wu, Chaim Yosefy, Anwer Qureshi, and Sarah Chua
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Male ,medicine.medical_specialty ,Short axis ,Echocardiography, Three-Dimensional ,Standard deviation ,Mean difference ,Internal medicine ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Observer Variation ,Ejection fraction ,Ventricular function ,business.industry ,Three dimensional echocardiography ,General Medicine ,Middle Aged ,Rv function ,Cardiology ,Linear Models ,Ventricular Function, Right ,Female ,Clinical/Original Papers ,Cardiology and Cardiovascular Medicine ,business ,Apical four chamber view - Abstract
Aims Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE. Methods and results Twenty-five patients underwent 2DE and RT3DE. Views of 2DE (RV inflow, RV short axis, and apical four-chamber) were compared with RT3DE views by four readers. RT3DE data sets were sliced from anterior–posterior (apical view) and from base to apex (short axis) to obtain six standardized planes. Readers recorded the RV ejection fraction (RVEF) from 2DE and RT3DE images. RVEF recorded by RT3DE (RVEF3D) and 2D (RVEF2D) were compared with RVEF by disc summation (RVEFDS), which was used as a reference. Interobserver variability among readers of RVEF3D and RVEF2D was then compared. Overall, mean RVEFDS, RVEF3D, and RVEF2D were 37 ± 11%, 38 ± 10%, 41 ± 10%, respectively. The mean difference of RVEF3D − RVEFDS was significantly less than RVEF2D–RVEFDS (3.7 ± 4% vs. 7.1 ± 5%, P = 0.0066, F -test). RVEF3D correlated better with RVEFDS ( r = 0.875 vs. r = 0.69, P = 0.028, t -test). RVEF3D was associated with a 39% decrease in interobserver variability when compared with RVEF2D [standard deviation of mean difference: 3.7 vs. 5.1, (RT3DE vs. 2DE), P = 0.018, t -test]. Conclusions RT3DE provides improved accuracy of RV function assessment and decreases interobserver variability when compared with 2D views.
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- 2009
14. Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation
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Steve Leu, Fan-Yen Lee, Hon-Kan Yip, Sheng-Ying Chung, Kuo-Ho Yeh, Tzu-Hsien Tsai, Yung-Lung Chen, Chiung-Jen Wu, Chia-Lo Chang, Sarah Chua, Cheuk-Kwan Sun, Chia-Hung Yen, and Jiunn-Jye Sheu
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CD31 ,Male ,medicine.medical_specialty ,Angiogenesis ,Ischemia ,CD34 ,Adipose tissue ,lcsh:Medicine ,Fluorescent Antibody Technique ,Neovascularization, Physiologic ,General Biochemistry, Genetics and Molecular Biology ,Neovascularization ,Mice ,Cytosol ,Cell Movement ,Internal medicine ,Obesity control ,Laser-Doppler Flowmetry ,Medicine ,Animals ,Obesity ,Progenitor cell ,Endothelial progenitor cells ,Medicine(all) ,Inflammation ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Stem Cells ,lcsh:R ,Critical limb ischemia ,Cytochromes c ,Endothelial Cells ,General Medicine ,medicine.disease ,Fibrosis ,Hindlimb ,Mitochondria ,Endothelial stem cell ,Oxidative Stress ,Endocrinology ,Adipose Tissue ,Regional Blood Flow ,medicine.symptom ,business ,Biomarkers - Abstract
Background and aim We tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs), angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control. Methods 8-week-old C57BL/6J mice (n = 27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks. Results Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p Conclusion Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.
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- 2012
15. Sitagliptin attenuated brain damage and cognitive impairment in mice with chronic cerebral hypo-perfusion through suppressing oxidative stress and inflammatory reaction.
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Tzu-Hsien Tsai, Cheuk-Kwan Sun, Chai-Hao Su, Pei-Hsun Sung, Sarah Chua, Yen-Yi Zhen, Steve Leu, Hsueh-Wen Chang, Jenq-Lin Yang, and Hon-Kan Yip
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- 2015
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16. VEGF tonically sustains myocardial performance via fetal liver kinase-1 in the heart.
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Ching-Yi Tsai, Sarah Chua, Steve Leu, Alice Y.W. Chang, Julie Y.H. Chan, and Samuel H.H. Chan
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VASCULAR endothelial growth factors , *MYOCARDIAL infarction , *FETAL liver cells , *KINASES , *ECHOCARDIOGRAPHY , *HYPERTENSION - Published
- 2014
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17. Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy.
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Jiunn-Jye Sheu, Pao-Yuan Lin, Pei-Hsun Sung, Yi-Ching Chen, Steve Leu, Yung-Lung Chen, Tzu-Hsien Tsai, Han-Tan Chai, Sarah Chua, Hsueh-Wen Chang, Sheng-Ying Chung, Chih-Hung Chen, Sheung-Fat Ko, and Hon-Kan Yip
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LIPOPROTEINS ,GALECTINS ,ISCHEMIA ,CLOPIDOGREL ,GENE expression - Abstract
Objective 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). Methods A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and kidney injury in sepsis syndrome caused by cecal ligation puncture in rats.
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Pei-Hsun Sung, Chia-Lo Chang, Tzu-Hsien Tsai, Li-Teh Chang, Steve Leu, Yung-Lung Chen, Chic-Chao Yang, Sarah Chua, Kuo-Ho Yeh, Han-Tan Chai, Hsueh-Wen Chang, Hong-Hwa Chen, and Hon-Kan Yip
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Introduction: 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. Methods: 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. Results: 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). Conclusions: A-ADMSC therapy was superior to H-ADMSC therapy in protecting major organs from damage in rats with CLP-induced sepsis syndrome. [ABSTRACT FROM AUTHOR]
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- 2013
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19. Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity.
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Jiunn-Jye Sheu, Pei-Hsun Sung, Steve Leu, Han-Tan Chai, Yen-Yi Zhen, Yi-Ching Chen, Sarah Chua, Yung-Lung Chen, Tzu-Hsien Tsai, Fan-Yen Lee, Hsueh-Wen Chang, Sheung-Fat Ko, and Hon-Kan Yip
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IMMUNE response ,MYOCARDIAL infarction ,ANTI-infective agents ,TACROLIMUS ,MAGNETIC resonance imaging ,BIOMARKERS - Abstract
Background 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 AMITacrolimus (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. Results 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-α, NF-κB, 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 [γ-H2AX, β-myosin heavy chain (MHC), Smad3, TGF-β] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, α-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001). Conclusion Innate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment. [ABSTRACT FROM AUTHOR]
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- 2013
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20. Sitagliptin therapy enhances the number of circulating angiogenic cells and angiogenesis–evaluations in vitro and in the rat critical limb ischemia model.
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SARAH CHUA, JIUNN-JYE SHEU, YUNG-LUNG CHEN, LI-TEH CHANG, CHEUK-KWAN SUN, STEVE LEU, HSIN-CHING SUNG, TZU-HSIEN TSAI, SHENG-YING CHUNG, KUO-HO YEH, CHUNG-LUNG CHO, YING-HSIEN KAO, and HON-KAN YIP
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SITAGLIPTIN , *LABORATORY rats , *ANIMAL models of ischemia , *NEOVASCULARIZATION , *LASER Doppler blood flowmetry , *PROGENITOR cells , *IMMUNOHISTOCHEMISTRY - Abstract
Background aims. We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CU) model by enhancement of angiogenesis. Methods. 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). Results. In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-l/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-l+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P < 0.00 1). 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+, CD3 1+, 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). Conclusions. Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area. [ABSTRACT FROM AUTHOR]
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- 2013
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21. Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.
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Yen-Ta Chen, Chih-Chau Yang, Yen-Yi Zhen, Wallace, Christopher Glenn, Jenq-Lin Yang, Cheuk-Kwan Sun, Tzu-Hsien Tsai, Jiunn-Jye Sheu, Sarah Chua, Chia-Lo Chang, Chung-Lung Cho, Leu, Steve, and Hon-Kan Yip
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CYCLOSPORINE ,STEM cells ,CREATINE ,HETEROCYCLIC compounds ,CYCLIC peptides ,GLUTATHIONE - Abstract
Introduction: This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury to either therapy alone. Methods: Adult Sprague-Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×10
6 ) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). Results: By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2-associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P <0.05 for inter-group comparisons). Conclusion: Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury. [ABSTRACT FROM AUTHOR]- Published
- 2013
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22. Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction.
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Yen-Ta Chen, Cheuk-Kwan Sun, Yu-Chun Lin, Li-Teh Chang, Yung-Lung Chen, Tzu-Hsien Tsai, Sheng-Ying Chung, Sarah Chua, Ying-Hsien Kao, Chia-Hung Yen, Pei-Lin Shao, Kuan-Cheng Chang, Steve Leu, Hon-Kan Yip, Chen, Yen-Ta, Sun, Cheuk-Kwan, Lin, Yu-Chun, Chang, Li-Teh, Chen, Yung-Lung, and Tsai, Tzu-Hsien
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OXIDATIVE stress ,REACTIVE oxygen species ,ISCHEMIA ,REPERFUSION injury ,STEM cells - Abstract
Background: Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.Methods: Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.Results: Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)Conclusion: ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]- Published
- 2011
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23. Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction.
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Steve Leu, Ying-Hsien Kao, Cheuk-Kwan Sun, Yu-Chun Lin, Tzu-Hsien Tsai, Li-Teh Chang, Sarah Chua, Kuo-Ho Yeh, Chiung-Jen Wu, Morgan Fu, and Hon-Kan Yip
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MYOCARDIAL infarction ,EXTRACELLULAR matrix proteins ,FIBROBLASTS ,INTRAVENOUS therapy ,BLOOD coagulation factors - Abstract
Background: We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model. Methods: Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h. Results: In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05). Conclusion: MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model. [ABSTRACT FROM AUTHOR]
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- 2011
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24. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilatedcardiomyopathy.
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Yu-Chun Lin, Steve Leu, Cheuk-Kwan Sun, Chia-Hung Yen, Ying-Hsien Kao, Li-Teh Chang, Tzu-Hsien Tsai, Sarah Chua, Morgan Fu, Sheung-Fat Ko, Chiung-Jen Wu, Fan-Yen Lee, and Hon-Kan Yip
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SILDENAFIL ,MYOCARDIUM ,FIBROSIS ,APOPTOSIS ,ADIPOSE tissues - Abstract
Background: We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC) and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM). Methods: Adult Lewis rats (n = 8 per group) were divided into group 1 (normal control), group 2 (saline-treated DCM rats), group 3 [2.0 x 10
6 ADMSC implanted into left ventricular (LV) myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally), and group 5 (DCM rats with combined ADMSC-sildenafil). Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. Results: The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p < 0.002). Conversely, oxidative index was highest in group 2, and also higher in groups 3 and 4 than in group 5 (p < 0.0003). The mRNA expressions of interleukin (IL)- 10, Gro/IL-8, endothelial nitric oxide synthase, and Bcl-2 were lowest in group 2, and lower in groups 3 and 4 compared with group 5 (p < 0.0001). The mRNA expressions of matrix metalloproteinase-9, Bax, caspase 3, and stromal-cell derived factor-1α were highest in group 2, and higher in groups 3 and 4 than in group 5 (p < 0.0004). Apoptosis and fibrosis in LV myocardium were most prominent in group 2 and higher in groups 3 and 4 than in group 5, whereas angiogenesis and LV ejection fraction were lowest in group 2 and lower in groups 3 and 4 than in group 5 (p < 0.003). Conclusion: Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function. [ABSTRACT FROM AUTHOR]- Published
- 2010
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25. Levels and Values of Serum High-Sensitivity C-Reactive Protein Within 6 Hours After the Onset of Acute Myocardial Infarction.
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Hon-Kan Yip, Chiung-Jen Wu, Hsueh- Wen Chang, Cheng-Hsu Yang, Kuo-Ho Yeh, Sarah Chua, and Morgan Fu
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C-reactive protein ,PLAQUES & plaquettes ,SERUM ,MYOCARDIAL infarction ,GLOBULINS ,ACUTE phase proteins - Abstract
Background: C-reactive protein (CRP), which has been suggested to directly enhance inflammation in plaques, is rapidly synthesized and secreted in the liver 6 h after an acute inflammatory stimulus. Therefore, serum levels of CRP within 6 h after the onset of acute myocardial infarction (AMI) merely reflect a chronic and persistent inflammatory process and are not due to acute myocardial damage. We hypothesized that the serum CRP level, which would abnormally elevate thereafter, is followed by a plaque rupture in the clinical setting of AMI. Methods and results: CRP was prospectively measured by high-sensitivity CRP assay (hs-CRP) in 157 consecutive patients (106 patients within 6 h, and 51 patients ⩾ 6 h but < 12 h after the onset of AMI) with ST-segment elevation AMI undergoing primary percutaneous coronary intervention (PCI). Serum levels of hs-CRP were also measured in 30 patients with stable angina undergoing elective PCI and in 30 healthy control subjects. The serum level of hs-CRP was significantly higher in patients with an onset of AMI < 6 h than in patients with angina pectoris (2.7 ± 2.3 mg/L vs 1.4 ± 0.7 mg/L, p < 0.0001 [mean ± SD]) and in healthy subjects (2.7 ± 2.3 mg/L vs 1.0 ± 0.6 mg/L, p < 0.0001). There were no significant differences in serum levels of hs-CRP in patients with an onset of AMI > 3 h than in those patients with an onset of AMI > 3 h but < 6 h (2.7 ± 2.5 mg/L vs 2.7 ± 2.2 mg/L, p = 0.87). However, the serum level of hs-CRP was significantly higher in patients with an onset < 6 h than in patients with an onset < 6 h (14.1 ± 16.5 mg/L vs 2.7 ± 2.3 mg/L, p < 0.0001). Conclusions: Serum levels of hs-CRP were significantly higher in patients with an onset of AMI < 6 h than in healthy subjects and in patients with angina pectoris undergoing PCI. The inflammatory process has been proved as one of the mechanisms causing plaque rupture. Elevated serum hs-CRP levels in patients with AMI < 6 h may portend vulnerable plaque rupture. [ABSTRACT FROM AUTHOR]
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- 2004
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26. Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats
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Tzu-Hsien Tsai, Cheuk-Kwan Sun, Jiunn-Jye Sheu, Yung-Lung Chen, Hon-Kan Yip, Steve Leu, Sarah Chua, Han-Tan Chai, Chu-Feng Liu, Hung-I Lu, Fan-Yen Lee, and Hsueh-Wen Chang
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Male ,Dipeptidyl Peptidase 4 ,Ischemia-reperfusion injury ,Myocardial Reperfusion Injury ,Inflammation ,Anterior Descending Coronary Artery ,Pharmacology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Dipeptidyl peptidase ,medicine ,Sitagliptin ,Animals ,Medicine(all) ,Dipeptidyl-Peptidase IV Inhibitors ,biology ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Dipeptidyl peptidase-IV (DPP4) enzyme ,General Medicine ,Heart function ,medicine.disease ,Rats, Inbred F344 ,Enzyme assay ,Rats ,Oxidative stress ,biology.protein ,medicine.symptom ,Ligation ,business ,Reperfusion injury ,medicine.drug - Abstract
Background We investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion). Methods and results Adult male Fischer 344 rats (n = 24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4D) rats (n = 16) were equally divided into DPP4D-SC and DPP4D-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (H&E), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4D-IR groups than in WT-SC and DPP4D-SC groups (all p
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27. Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice
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Chu-Feng Liu, Tzu-Hsien Tsai, Hsueh-Wen Chang, Sarah Chua, Chia-Hung Yen, Yung-Lung Chen, Steve Leu, Hon-Kan Yip, Hui-Ting Wang, Yen-Yi Zhen, Ching-Yen Tsai, Han-Tan Chai, and Sheng-Ying Chung
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Male ,medicine.medical_specialty ,Heart Ventricles ,lcsh:Medicine ,Mice, Obese ,Inflammation ,Apoptosis ,medicine.disease_cause ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Weight loss ,Fibrosis ,Internal medicine ,Weight Loss ,medicine ,Animals ,Obesity ,RNA, Messenger ,Ventricular remodeling ,Ultrasonography ,Medicine(all) ,Ejection fraction ,Adiponectin ,Ventricular Remodeling ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Leptin ,Myocardium ,Research ,lcsh:R ,General Medicine ,medicine.disease ,Oxidative Stress ,Endocrinology ,Vasoconstriction ,Heart Function Tests ,medicine.symptom ,business ,Reactive Oxygen Species ,Oxidative stress ,Biomarkers - Abstract
Background Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice. Methods and results Eight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p Conclusion Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.
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28. Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction
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Sarah Chua, Steve Leu, Yu-Chun Lin, Li-Teh Chang, Kuo-Ho Yeh, Morgan Fu, Cheuk-Kwan Sun, Chiung-Jen Wu, Ying-Hsien Kao, Hon-Kan Yip, and Tzu-Hsien Tsai
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Male ,medicine.medical_specialty ,Cardiac fibrosis ,Myocardial Infarction ,lcsh:Medicine ,medicine.disease_cause ,Models, Biological ,Collagen Type I ,Ventricular Function, Left ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Left coronary artery ,Von Willebrand factor ,Internal medicine ,medicine.artery ,medicine ,Animals ,Myocardial infarction ,Cells, Cultured ,Medicine(all) ,Ejection fraction ,biology ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Myocardium ,Research ,lcsh:R ,General Medicine ,Fibroblasts ,medicine.disease ,Actins ,Matrix Metalloproteinases ,Rats ,Vascular endothelial growth factor ,Animals, Newborn ,Gene Expression Regulation ,chemistry ,Culture Media, Conditioned ,biology.protein ,Cardiology ,business ,Ligation ,Oxidative stress - Abstract
Background We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model. Methods Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h. Results In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05). Conclusion MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.
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29. Intra-coronary administration of tacrolimus markedly attenuates infarct size and preserves heart function in porcine myocardial infarction
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Yu-Chun Lin, Yung-Lung Chen, Hon-Kan Yip, Hsueh-Wen Chang, Steve Leu, Tzu-Hsien Tsai, Sarah Chua, Cheuk-Kwan Sun, Ying-Hsien Kao, Li-Teh Chang, Chia-Hung Yen, and Jiunn-Jye Sheu
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Research ,Clinical Biochemistry ,Pharmacology toxicology ,lcsh:RM1-950 ,Cell Biology ,Anterior Descending Coronary Artery ,Infarct size ,medicine.disease ,Tacrolimus ,lcsh:Therapeutics. Pharmacology ,Internal medicine ,medicine ,Cardiology ,Myocardial infarction ,cardiovascular diseases ,business - Abstract
Background We test the hypothesis that intra-coronary tacrolimus administration can limit infarct size and preserve left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) through ligating left anterior descending coronary artery (LAD) in mini-pigs. Methods Twelve male mini-pigs were randomized into AMI-saline (MI-only) group and AMI-tacrolimus (MI-Tac) group that received intra-coronary saline (3.0 mL) and tacrolimus (0.5 mg in 2.5 mL saline) injection, respectively, beyond site of ligation 30 minutes after LAD occlusion. Results Larger infarct area was noted in MI-only group (p Conclusion Intra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function.
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30. Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy
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Hon-Kan Yip, Sheung-Fat Ko, Pao-Yuan Lin, Jiunn-Jye Sheu, Hsueh-Wen Chang, Chih-Hung Chen, Yi-Ching Chen, Tzu-Hsien Tsai, Sarah Chua, Steve Leu, Pei-Hsun Sung, Yung-Lung Chen, Sheng-Ying Chung, and Han-Tan Chai
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Male ,Ticlopidine ,Combination therapy ,Galectin 3 ,Ischemia ,Tetrazoles ,Pharmacology ,Endothelial progenitor cell ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Humans ,Progenitor cell ,Endothelial progenitor cells ,Aged ,DNA Primers ,Inflammation ,Medicine(all) ,rho-Associated Kinases ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Lipoprotein-associated phospholipase A2 ,Critical limb ischemia ,Extremities ,Cilostazol therapy ,General Medicine ,medicine.disease ,Cilostazol ,Clopidogrel ,body regions ,1-Alkyl-2-acetylglycerophosphocholine Esterase ,Platelet aggregation inhibitor ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,Platelet Aggregation Inhibitors ,circulatory and respiratory physiology ,medicine.drug - Abstract
Objective 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). Methods A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. Results As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p
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31. Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia–reperfusion injury
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Jiunn-Jye Sheu, Cheuk-Kwan Sun, Steve Leu, Tzu-Hsien Tsai, Chih-Chau Yang, Jenq-Lin Yang, Yen-Yi Zhen, Chung-Lung Cho, Chia-Lo Chang, Sarah Chua, Yen-Ta Chen, Hon-Kan Yip, and Christopher Glenn Wallace
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Male ,medicine.medical_specialty ,Pathology ,Glutathione reductase ,Cell- and Tissue-Based Therapy ,Medicine (miscellaneous) ,Biology ,medicine.disease_cause ,Kidney ,Mesenchymal Stem Cell Transplantation ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Blood Urea Nitrogen ,Rats, Sprague-Dawley ,Bcl-2-associated X protein ,Internal medicine ,medicine ,Animals ,bcl-2-Associated X Protein ,chemistry.chemical_classification ,Caspase 3 ,Superoxide Dismutase ,Tumor Necrosis Factor-alpha ,Glutathione peroxidase ,Research ,Acute kidney injury ,Kidney metabolism ,Mesenchymal Stem Cells ,Cell Biology ,Acute Kidney Injury ,medicine.disease ,Rats ,Oxidative Stress ,Endocrinology ,chemistry ,Adipose Tissue ,Apoptosis ,Creatinine ,Reperfusion Injury ,biology.protein ,Cyclosporine ,Molecular Medicine ,Reperfusion injury ,Oxidative stress ,DNA Damage - Abstract
Introduction This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia–reperfusion (IR) kidney injury to either therapy alone. Methods Adult Sprague–Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). Results By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P 0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P
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32. Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views.
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Sarah Chua, Robert A. Levine, Chaim Yosefy, Mark D. Handschumacher, John Chu, Anwer Qureshi, Jennifer Neary, Thanh-Thao Ton-Nu, Morgan Fu, Chiung Jen Wu, and Judy Hung
- Abstract
: Aims Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE. : Methods and results Twenty-five patients underwent 2DE and RT3DE. Views of 2DE (RV inflow, RV short axis, and apical four-chamber) were compared with RT3DE views by four readers. RT3DE data sets were sliced from anterior–posterior (apical view) and from base to apex (short axis) to obtain six standardized planes. Readers recorded the RV ejection fraction (RVEF) from 2DE and RT3DE images. RVEF recorded by RT3DE (RVEF
3D ) and 2D (RVEF2D ) were compared with RVEF by disc summation (RVEFDS ), which was used as a reference. Interobserver variability among readers of RVEF3D and RVEF2D was then compared. Overall, mean RVEFDS , RVEF3D , and RVEF2D were 37 ± 11%, 38 ± 10%, 41 ± 10%, respectively. The mean difference of RVEF3D − RVEFDS was significantly less than RVEF2D –RVEFDS (3.7 ± 4% vs. 7.1 ± 5%, P = 0.0066, F-test). RVEF3D correlated better with RVEFDS (r = 0.875 vs. r = 0.69, P = 0.028, t-test). RVEF3D was associated with a 39% decrease in interobserver variability when compared with RVEF2D [standard deviation of mean difference: 3.7 vs. 5.1, (RT3DE vs. 2DE), P = 0.018, t-test]. : Conclusions RT3DE provides improved accuracy of RV function assessment and decreases interobserver variability when compared with 2D views. [ABSTRACT FROM AUTHOR]- Published
- 2009
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33. Combined therapy with shock wave and autologous bone marrow-derived mesenchymal stem cells alleviates left ventricular dysfunction and remodeling through inhibiting inflammatory stimuli, oxidative stress & enhancing angiogenesis in a swine myocardial infarction model.
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Jiunn-Jye Sheu, Fan-Yen Lee, Chun-Man Yuen, Yi-Ling Chen, Tien-Hung Huang, Sarah Chua, Yung-Lung Chen, Chih-Hung Chen, Han-Tan Chai, Pei-Hsun Sung, Hsueh-Wen Chang, Cheuk-Kwan Sun, and Hon-Kan Yip
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LEFT heart ventricle diseases , *INFLAMMATION , *SHOCK waves , *MESENCHYMAL stem cells , *OXIDATIVE stress , *STIMULUS & response (Biology) , *NEOVASCULARIZATION , *LABORATORY swine - Abstract
Background We hypothesized that combined therapy with shock wave (SW) and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) is superior to either therapy alone for alleviating left ventricular (LV) dysfunction. Methods and results Male mini-pigs (n = 30) equally divided into group 1 (sham control), group 2 [acute myocardial infarction (AMI) by left coronary artery ligation], group 3 (AMI-SW), group 4 (AMI-BMDMSC), and group 5 (AMI-SW-BMDMSC) were sacrificed by day 60 and the hearts were collected for studies. Baseline LV injection fraction [LVEF (%)] and LV chamber size did not differ among the five groups (p > 0.5). By day 60, LVEF was highest in group 1 and lowest in group 2, significantly higher in group 5 than that in groups 3 and 4, and significantly higher in group 4 than that in group 3 (p < 0.001). Cellular and protein levels of VEGF, CXCR4, and SDF-1a were significantly increased progressively from groups 1 to 5 (all p < 0.05). Small vessel number and protein expressions of CD31 and eNOS were highest in groups 1 and 5, lowest in group 2, and significantly higher in group 4 than those in group 3 (p < 0.001). Protein (MMP-9, TNF-1a and NF-?B) and cellular (CD14 +, CD40 +) levels of inflammatory biomarkers, protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), apoptosis (Bax, caspase-3, PARP), infarct size, and LV dimensions showed a pattern opposite to that of LVEF among all groups (all p < 0.001). Conclusions Combined SW-BMDMSC therapy is superior to either therapy alone for improving LVEF, reducing infarct size, and inhibiting LV remodeling. [ABSTRACT FROM AUTHOR]
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- 2015
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