| Summary: | 博士 === 高雄醫學大學 === 醫學研究所博士班 === 104 === Arrhythmias remain a major cause of death and major morbidities for patients with cardiovascular diseases. Regular and functional cardiac rhythm is based on the rhythmic synchrony of cardiac action potentials throughout the whole heart. To understand how cardiac action potentials are triggered and propagated is fundamental for studying mechanisms of arrhythmias.
Cardiac action potentials are driven by a diversity of currents via different ion channels, one of them is the slow delayed rectifier potassium channel current (IKs) in which the α-subunits are encoded by KCNQ1 gene. Alternative splicing isoform KCNQ1b exerts dominant negative effect on IKs and increased KCNQ1b may significantly reduce IKs current density. For the first time, this study demonstrated KCNQ1 splicing forms are differentially changed by amiloride treatment in cardiac ventricle and as a result the arrhythmogeneity is affected. Two study modalities, patch clamp experiments and computational simulations were combined and were carried out at the Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in Saint Louis, Missouri during my study abroad from September 2010 to July 2012.
Returning back from the States, the research was re-initiated at a brand new teaching building. I built up things in an empty room and started to study about the lipids. Metabolic syndrome (MetS) represents a cluster of metabolic derangements and contributes many of cardiovascular diseases. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). Therefore I hypothesized that the very low density lipoproteins (VLDL) in MetS (MetS-VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. A new mice model was created. With MetS-VLDL injection to wild type C57BL/6 male mice for six consecutive weeks, mice developed significant left atrial dilation. Unprovoked AF occurred in elderly MetS-VLDL injection mice. Excess lipid accumulation and apoptosis in msVLDL mice atria suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals. The study had been carried out during the building up of our own basic heart electrophysiological laboratory, from November 2013 to September 2015.
The two major findings in this thesis both offer novel insights for unclear field in the mechanisms of arrhythmias.
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