Translational Study of Cardiac Dysfunction

摘要 房颤(房颤)是临床上最常见的心律失常之一，与 发病率和死亡率显著增加，然而，目前的治疗模式仍然不足。治疗 与传统的抗心律失常药物相比，通常具有较高的致心律失常风险。此外，流行性出血热 由于人口老龄化，房颤正在增加。我们是第一个展示小说有益效果的人 一类抗炎药，可溶性环氧化物水解酶(SEH)抑制剂，在临床相关模型中的应用 心肌肥大和衰竭。使用sEH抑制剂(SEHIs)可预防脑室出血 压力超负荷和心肌梗死模型中的心肌细胞肥大和电重构。在上一次资助期间 周期中，我们证明使用sEHIs治疗可以预防心脏成纤维细胞(CF)的增殖、纤维化、不良反应 心脏重构和房颤。这些结果显示了心脏重塑的更广泛的有益作用(不是 仅限于心肌细胞肥大)这类新化合物。竞争性更新的目标是 为了检验这样一种假设，即sEHIS增加内源性EET水平代表完全 未探索的途径是通过减少CF的增殖和激活来改善心房纤维化。这项建议 这是一项从床到床的多学科研究，旨在确定使用sEHIs的机制和有效性。 用于治疗房颤。

Abstract Atrial fibrillation (AF) represents one of the most common arrhythmias clinically and is associated with a significant increase in morbidity and mortality, yet, current treatment paradigms remain inadequate. Treatment with conventional antiarrhythmic drugs generally carries a high risk of proarrhythmia. Moreover, prevalence of AF is increasing due to the aging population. We were the first to demonstrate beneficial effects of a novel class of anti-inflammatory agent, soluble epoxide hydrolase (sEH) inhibitors, in clinically relevant models of cardiac hypertrophy and failure. Treatment with sEH inhibitors (sEHIs) results in the prevention of ventricular myocyte hypertrophy and electrical remodeling in pressure overload and MI models. During the last funding cycle, we demonstrate that treatment with sEHIs prevents cardiac fibroblast (CF) proliferation, fibrosis, adverse cardiac remodeling, and AF. These results demonstrate broader salutary effects in cardiac remodeling (not limited to myocyte hypertrophy alone) of this novel class of compounds. The goal of the competing renewal is to test the hypothesis that an increase in the level of endogenous EETs by sEHIs represents a completely unexplored avenue to modify atrial fibrosis by reducing CF proliferation and activation. The proposal represents a bench-to-bedside multidisciplinary study to determine the mechanism and efficacy of using sEHIs for the treatment of AF.