Browsing by Author "Chang, Chia-Chu"

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Decrease in Plasma Cyclophilin A Concentration at 1 Month after Myocardial Infarction Predicts Better Left Ventricular Performance and Synchronicity at 6 Months: A Pilot Study in Patients with ST Elevation Myocardial Infarction
(2015-01-01)
Huang, Ching-Hui
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Chang, Chia-Chu
;
Kuo, Chen-Ling
;
Huang, Ching-Shan
;
Lin, Chih-Sheng
Background: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-,three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 +/- 11.5% to 64.6 +/- 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 +/- 0.510% to 1.637 +/- 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI. Conclusions: Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome.
Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles
(2018-01-01)
Chang, Hui-Fang
;
Sun, Yu-Ling
;
Yeh, Fang-Yuan
;
Tseng, I-Hua
;
Chang, Chia-Chu
Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL(-1) of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.
Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session
(2017-11-20)
Yang, Chung-Wei
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Lu, Li-Che
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Chang, Chia-Chu
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Cho, Ching-Chang
;
Hsieh, Wen-Yeh
Background: The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. Methods: There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. Results: We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. Conclusions: Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.
Imbalanced Plasma ACE and ACE2 ratio in the Uremic Patients with Cardiovascular Diseases and Its Change during a Single Hemodialysis Session
(2017-04-01)
Cho, Ching-Chang
;
Lu, Li-Che
;
Chang, Chia-Chu
;
Lin, Chung-I
;
Wang, Guan-Hua
Renal chymase-dependent pathway for angiotensin II formation mediated acute kidney injury in a mouse model of aristolochic acid I-induced acute nephropathy
(2019-01-11)
Hsieh, Wen-Yeh
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Chang, Teng-Hsiang
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Chang, Hui-Fang
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Chuang, Wan-Hsuan
;
Lu, Li-Che
Angiotensin-converting enzyme (ACE) is the primary enzyme that converts angiotensin I (Ang I) to angiotensin II (Ang II) in the renin-angiotensin system (RAS). However, chymase hydrates Ang I to Ang II independently of ACE in some kidney diseases, and it may play an important role. The present study investigated whether chymase played a crucial role in aristolochic acid I (AAI)-induced nephropathy. C57BL/6 mice were treated with AAI via intraperitoneal injection for an accumulated AAI dosage of 45 mg/kg body weight (BW) (15 mg/kg BW per day for 3 days). The animals were sacrificed after acute kidney injury development, and blood, urine and kidneys were harvested for biochemical and molecular assays. Mice exhibited increased serum creatinine, BUN and urinary protein after the AAI challenge. Significant infiltrating inflammatory cells and tubular atrophy were observed in the kidneys, and high immunocytokine levels were detected. Renal RAS-related enzyme activities were measured, and a significantly increased chymase activity and slightly decreased ACE activity were observed in the AAI-treated mice. The renal Ang II level reflected the altered profile of RAS enzymes and was significantly increased in AAI-treated mice. Treatment of AAI-induced nephropathic mice with an ACE inhibitor (ACEI) or chymase inhibitor (CI; chymostatin) reduced renal Ang II levels. The combination of ACEI and CI (ACEI+CI) treatment significantly reversed the AAI-induced changes of Ang II levels and kidney inflammation and injuries. AAI treatment significantly increased renal p-MEK without increasing p-STAT3 and p-Smad3 levels, and p-MEK/p-ERK1/2 signalling pathway was significantly activated. CI and ACEI+CI treatments reduced this AAI-activated signaling pathway. AAI-induced nephropathy progression was significantly mitigated with CI and ACEI+CI treatment. This study elucidates the role of RAS in the pathogenesis of AAI-induced nephropathy.
Serum Iron Concentration, but Not Hemoglobin, Correlates with TIMI Risk Score and 6-Month Left Ventricular Performance after Primary Angioplasty for Acute Myocardial Infarction
(2014-08-06)
Huang, Ching-Hui
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Chang, Chia-Chu
;
Kuo, Chen-Ling
;
Huang, Ching-Shan
;
Chiu, Tzai-Wen
Objective: Anemia is associated with high mortality and poor prognosis after acute coronary syndrome (A(S). Increased red cell distribution width (RDW) is a strong independent predictor for adverse outcomes in ACS. The common underlying mechanism for anemia and increased RDW value is iron deficiency. It is not clear whether serum iron deficiency without anemia affects left ventricular (LV) performance after primary angioplasty for acute myocardial infarction (AMI). We investigated the prognostic value of serum iron concentration on LV ejection fraction (EF) at 6 months and its relationship to thrombolysis in myocardial infarction (TIMI) risk score in post MI patients. Methods: We recruited 55 patients who were scheduled to undergo primary coronary balloon angioplasty after AM I and 54 age- and sex-matched volunteers. Serum iron concentration and interleukin-6 levels were measured before primary angioplasty. LVEF was measured by echocardiography at baseline and after 6 months. TIMI risk score was calculated for risk stratification. Results: Serum iron concentration was significantly lower in those in whom LVEF had not improved >= 10% from baseline (52.7 +/- 24.1 versus 80.8 +/- 50.8 mu g/dl, P = 0.016) regardless of hemoglobin level, and was significantly lower in the AMI group than in the control group (62.5 +/- 37.7 versus 103.0 +/- 38.1 mu g/dl, P<0.001). Trend analysis revealed that serum iron concentration decreased as TIMI risk score increased (P = 0.002). In addition, lower serum iron concentrations were associated with higher levels of inflammatory markers. Multiple linear regression showed that baseline serum iron concentration can predict LV systolic function 6 months after primary angioplasty for AMI even after adjusting for traditional prognostic factors. Conclusion: Hypoferremia is not only a marker of inflammation but also a potential prognostic factor for LV systolic function after revascularization therapy for AMI, and may be a novel biomarker for therapeutic intervention.
Serum Iron Concentration, but Not Hemoglobin, Correlates with TIMI Risk Score and 6-Month Left Ventricular Performance after Primary Angioplasty for Acute Myocardial Infarction
(2014-08-06)
Huang, Ching-Hui
;
Chang, Chia-Chu
;
Kuo, Chen-Ling
;
Huang, Ching-Shan
;
Chiu, Tzai-Wen
Objective: Anemia is associated with high mortality and poor prognosis after acute coronary syndrome (A(S). Increased red cell distribution width (RDW) is a strong independent predictor for adverse outcomes in ACS. The common underlying mechanism for anemia and increased RDW value is iron deficiency. It is not clear whether serum iron deficiency without anemia affects left ventricular (LV) performance after primary angioplasty for acute myocardial infarction (AMI). We investigated the prognostic value of serum iron concentration on LV ejection fraction (EF) at 6 months and its relationship to thrombolysis in myocardial infarction (TIMI) risk score in post MI patients. Methods: We recruited 55 patients who were scheduled to undergo primary coronary balloon angioplasty after AM I and 54 age- and sex-matched volunteers. Serum iron concentration and interleukin-6 levels were measured before primary angioplasty. LVEF was measured by echocardiography at baseline and after 6 months. TIMI risk score was calculated for risk stratification. Results: Serum iron concentration was significantly lower in those in whom LVEF had not improved >= 10% from baseline (52.7 +/- 24.1 versus 80.8 +/- 50.8 mu g/dl, P = 0.016) regardless of hemoglobin level, and was significantly lower in the AMI group than in the control group (62.5 +/- 37.7 versus 103.0 +/- 38.1 mu g/dl, P<0.001). Trend analysis revealed that serum iron concentration decreased as TIMI risk score increased (P = 0.002). In addition, lower serum iron concentrations were associated with higher levels of inflammatory markers. Multiple linear regression showed that baseline serum iron concentration can predict LV systolic function 6 months after primary angioplasty for AMI even after adjusting for traditional prognostic factors. Conclusion: Hypoferremia is not only a marker of inflammation but also a potential prognostic factor for LV systolic function after revascularization therapy for AMI, and may be a novel biomarker for therapeutic intervention.
Tubular transcriptional co-activator with PDZ-binding motif protects against ischemic acute kidney injury
(2020-07-01)
Wu, Chia-Lin
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Chang, Chia-Chu
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Yang, Tao-Hsiang
;
Tsai, Alexander Charng-Dar
;
Wang, Jui-Lin
Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia-reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was up-regulated in RPTECs and the renal cortex or tubules. Up-regulation of TAZ in RPTECs subjected to hypoxia was controlled by I kappa B kinase (IKK)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappa B) signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and c-Jun N-terminal kinase (JNK) proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling, delayed wound closure of an RPTEC monolayer, and promoted G(0)/G(1) phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting (e.g., chloroquine) or suppressing (e.g., verteporfin) TAZ in the kidney might be beneficial or deleterious to patients with AKI.
Using Oxidized Low-Density Lipoprotein Autoantibodies to Predict Restenosis after Balloon Angioplasty in Patients with Acute Myocardial Infarction
(2013-10-03)
Huang, Ching-Hui
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Chang, Chia-Chu
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Huang, Ching-Shan
;
Kuo, Chen-Ling
;
Chen, Ching-Pei
Objectives: Oxidized low-density lipoproteins (oxLDL) and oxidized low-density lipoprotein autoantibodies (OLAB) have been detected in human plasma and atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL from circulation. Higher levels of OLAB appear to be associated with a reduced risk of a wide range of cardiovascular diseases. We investigated the prognostic value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon angioplasty for acute ST-elevation myocardial infarction (STEMI). Methods: Plasma oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI before primary angioplasty, and then 3 days, 7 days and 1 month after the acute event. Follow-up angiography was repeated 6 months later to detect the presence of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in myocardial infarction (TIMI) risk score was calculated to determine the relationship between OLAB/oxLDL ratio and TIMI risk scores. Results: Of the 56 patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB concentrations were significantly lower in the restenosis group before angioplasty (181 +/- 114 vs. 335 +/- 257 U/L, p = 0.003), and at day 3 (155 +/- 92 vs. 277 +/- 185 U/L, p<0.001) and day 7 (177 +/- 110 vs. 352 +/- 279 U/L, p<0.001) after the acute event. There was no difference in oxLDL concentration between the two groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores before angioplasty (p for trend analysis, p = 0.004), at day 3 (p = 0.008) and day 7 (p<0.001) after STEMI. Significance: A relative deficit of OLAB, and hence likely impaired clearance of oxLDL, is associated with the risk of arterial restenosis after primary angioplasty for acute STEMI.