| Summary: | 博士 === 國立交通大學 === 生物科技學系 === 107 === Chronic kidney disease (CKD) is a common and serious public health problem globally. Taiwan has the highest prevalence of end-stage renal disease (ESRD) in the world with 12% of adults affected by CKD. Numerous clinical studies have demonstrated excess cardiovascular risk is associated with CKD, and about half of CKD patients die from cardiovascular diseases. Novel therapeutic strategies showed some promising results, but morbidity and mortality of ESRD patients throughout the last decade did not decrease markedly. Therefore, exploring the underlying mechanisms for vasculopathy in CKD patients is essential to improve clinical outcomes.
MicroRNAs (miRs) are endogenous 20-22 nucleotides noncoding small RNAs that can act as endogenous RNA interference. MiRs are key regulators in cell function including endothelial cells, through regulating nitric oxide via eNOS, angiogenesis, and inflammation. For example, endothelial miR-126 and miR-483 are important regulators in angiogenesis and are required in endothelial repair and homeostasis. In addition to their intracellular functions, miRs can also be secreted through microparticles (MPs) for intercellular communication. An increase in endothelium-derived circulating MPs have been demonstrated in patients with ESRD and these MPs impair the NO-dependent vasodilation of rat aorta.
We tried to script the miRs roles in CKD patients through our study. First we will investigate circulating miRs in kidney injury mice model and patients. We wanted to identify possible miRs for kidney injury biomarker for clinicians to start treatment earlier. Second, given the prevalence of oxidative stress and endothelial dysfunction resulted from uremia in CKD, we will investigate whether miRs plays a pivotal role linking CKD and endothelial dysfunction. Finally we will investigate miR rols in neointimal hyperplasia in arterial-venous fistula for hemodialysis. These experiments may extend current knowledge and provide important information in clinical treatment.
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