Browsing by Author "Chen, Yi-Jen"

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Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia
(2015-06-15)
Tsai, Wen-Chin
;
Lu, Yen-Yu
;
Chen, Yao-Chang
;
Chang, Chien-Jung
;
Kao, Yu-Hsun
Background: Sex hormones and calcium (Ca2+) regulation play roles in the pathophysiology of ventricular tachycardia from right ventricular outflow tract (RVOT). The purpose of this study was to evaluate whether androgen receptor knockout (ARKO) can increase RVOT arrhythmogenesis through modulating RVOT electrophysiology and Ca2+ homeostasis. Methods: Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10 months) before and after caffeine (1 mM), isoproterenol (1 mu M), adenosine (10 mu M) and flecainide (5 mu M) administration. The Fluo-3 fluorescence Ca2+ imaging with confocal microscopy and western blots were used to investigate intracellular Ca2+ (Ca-i(2+)) transients, Ca2+ sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. Results: We found that ARKO RVOTs (n = 13) had longer AP duration, faster burst firing (5.4 +/- 0.7 vs. 3.4 +/- 0.7 Hz, P < 0.05), and higher incidence of early afterdepolarizations (82% vs. 8%, P < 0.001) than WT RVOTs (n = 11). Adenosine and flecainide can suppress caffeine-or isoproterenol-induced spontaneous rates and burst firing in WT RVOTs, but not in ARKO RVOTs. ARKO RVOT myocytes had a higher frequency (7.7 +/- 2.8 vs. 1.3 +/- 0.4 spark/mm/s, P < 0.05) and incidence (89% vs. 47%, P < 0.05) of Ca2+ sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO andWT RVOT myocytes exhibit similar Ca-i(2+) transients and SR Ca2+ content, and less expression of calsequestrin. Conclusions: ARKO changes RVOT electrophysiology and Ca2+ homeostasis with increased ventricular arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C) allorecognition patterns in women with endometriosis
(2020-03-17)
Chou, Ya-Ching
;
Chen, Chi-Huang
;
Chen, Ming-Jer
;
Chang, Ching-Wen
;
Chen, Pi-Hua
Endometriosis shares similarities with several autoimmune diseases. The human leukocyte antigen (HLA)-C genotype is associated with several human autoimmune diseases. HLA-C is a ligand of killer cell immunoglobulin receptors (KIRs) and is an essential regulator of natural killer cell activity, which is associated with endometriosis progression. Polymorphisms in HLA-C and KIR affect the activity of NK cells and susceptibility to several diseases. Therefore, we attempted to investigate an association between HLA-C genotype and KIR polymorphism and the occurrence of endometriosis. We tested the association of certain KIR and HLA-C combinations and the development of endometriosis by characterizing both KIR and HLA-C genes in 147 women with endometriosis and 117 controls. The HLA-C genotypes and KIR polymorphisms were analyzed via DNA-based method for higher-resolution genotyping. We found that the occurrence of HLA-C*03:03*01 was increased in endometriosis than in control groups. Analysis of various KIR haplotypes revealed differences between the endometriosis and control cohorts. The number of KIR centromeric A/A haplotypes was increased in the endometriosis group than controls. Moreover, the endometriosis cohort was characterized by reduced number of KIR2DS2-positive individuals in the Han Chinese population. Our current findings suggest that the KIR and HLA-C genotypes are associated with the pathogenesis of endometriosis.
Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia
(2016-12-14)
Weng, Ching-Hui
;
Chung, Fa-Po
;
Chen, Yao-Chang
;
Lin, Shien-Fong
;
Huang, Po-Hsun
Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage.
Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis
(2015-04-01)
Chang, Chien-Jung
;
Cheng, Chen-Chuan
;
Yang, Ten-Fang
;
Chen, Yao-Chang
;
Lin, Yung-Kuo
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. Methods: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. Results: Celecoxib (0.3, 1, and 3 mu M) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p < 0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 mu M) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 mu M) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 mu M) suppressed celecoxib (3 mu M)-induced PV burst firings in 6 (86%, p < 0.05) of 7 PVs. KB-R7943 (10 mu M) suppressed celecoxib (3 mu M)-induced PV burst firings in 5 (71%, p < 0.05) of 7 PVs. Conclusions: Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium
(2014-01-01)
Chang, Chien-Jung
;
Yang, Ten-Fang
;
Lee, Tin-I
;
Chen, Yao-Chang
;
Kao, Yu-Hsun
Background:The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. Methods: Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. Results: WKY (n = 5), SHR (n =7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptintreated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptintreated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. Conclusions: Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension.
The impact of microstructure end defects on moisture resistance of novel SiO(x)N(y) passivation layer for OLED applications
(2007-01-01)
Chen, Yi-Jen
;
Hsu, Kuo-Yuan
;
Chen, Yin-Ying
;
Su, Cheng-Feng
;
Tang, Shuenn-Jiun
The effects of grain boundaries in passivation layer and AI hillocks on moisture resistance were studied for SiO(x)N(y) thin films deposited by modified Ar ion beam evaporation. AI hillocks are attributed to be the culprit for moisture permeation, while its density and height dictate the required number layers of passivation for OLED applications.
The impact of microstructure end defects on moisture resistance of novel SiOxNy passivation layer for OLED applications
(2007-01-01)
Chen, Yi-Jen
;
Hsu, Kuo-Yuan
;
Chen, Yin-Ying
;
Su, Cheng-Feng
;
Tang, Shuenn-Jiun
The effects of grain boundaries in passivation layer and AI hillocks on moisture resistance were studied for SiOxNy thin films deposited by modified Ar ion beam evaporation. AI hillocks are attributed to be the culprit for moisture permeation, while its density and height dictate the required number layers of passivation for OLED applications.