Vascular Remodeling is a Crucial Factor in the Progression of Hypertrophic Cardiomyopathy

摘要： 我们对肥厚型心肌病早期不可逆进展和缺乏有效治疗的研究表明， 治疗使我们把注意力集中在冠状动脉微血管上。临床研究表明， 这种疾病中发生的有害的血管改变，但对潜在的 这种关系背后的机制一直很小。提案中提出的实验将 开始回答灌注和血管功能障碍在肥大性进展中所起的作用 心肌病考虑到这种疾病中的机械和能量缺陷，它们很可能阻碍了 生理性冠状动脉血流驱动血管重塑。这些关系和影响因素将是 更仔细地观察。心肌内的内皮功能障碍有望得到替代 主要血管扩张剂一氧化氮转化为ROS信号，这是血管功能障碍的典型表现。我们将 因此，努力了解血管活性分子之间的这种转换及其对冠状动脉粥样硬化的影响， 改变。最后，我们将尝试用一种新的方法来改变肥厚型心肌病的内皮功能。 鞘氨醇-1-磷酸类似物FTY 720，以防止早期建立的不可逆进展。

Abstract: Our investigations into the early irreversible progression in hypertrophic cardiomyopathy and the lack of effective treatments has led us to concentrate on the coronary microvasculature. Clinical studies have been characterizing the deleterious vascular alterations occurring in the disorder, but further investigations into the underlying mechanisms behind this relationship have been minimal. The experiments proposed within the proposal will begin to answer the role perfusion and vascular dysfunction play in the progression of hypertrophic cardiomyopathy. Given the mechanical and energetic deficiencies in the disorder, it is likely that they impede physiological coronary flow that drives remodeling of vessels. These relationships and influencing factors will be looked more closely into. The endothelial dysfunction within the myocardium is expected to have a substitution of the primary vasodilator nitric oxide to ROS signaling as is stereotypical of vascular dysfunction. We will therefore make efforts to understand this switch between vasoactive molecules and its impact on coronary alterations. We will lastly attempt to modify the endothelial function in hypertrophic cardiomyopathy with an sphingosine-1-phosphate analog, FTY720, to prevent the irreversible progression established early on.