Role of mesenchymal-endothelial-transition in cardiac hypertrophy

描述（由申请人提供）：我们最近描述了一种新的生物学现象，我们称之为间充质-内皮转化（MEEndoT），其中心脏中的瘢痕形成细胞在心脏损伤后表现出可塑性并采用内皮细胞样命运。成纤维细胞衍生的内皮细胞有助于损伤后新血管形成，并且破坏MEEndoT使损伤后新血管形成和修复恶化。相比之下，增加MEEndoT减少了纤维化并增强了心脏修复，证明了MEEndoT作为急性心脏损伤的新治疗靶点的潜力。在更慢性形式的心脏损伤如心脏肥大中，增加的新血管形成是心脏代偿反应的关键部分。增强的新血管形成见于初始代偿期，而血管退化和增加的纤维化见于心力衰竭发展之前的适应不良期。新生血管的破坏加速和增强新生血管延迟或延缓心脏肥大后心力衰竭的发展。然而，间充质-内皮转换是否发生在心肌肥厚中，并可作为延缓或延缓心力衰竭发展的治疗靶点还不清楚。在这项提案中，我们提供了初步的证据表明，间充质-内皮细胞转化发生在心脏肥大和询问的生理作用，MEEndoT在心脏肥大的增益和功能丧失的方法。我们的实验将提供新的洞察MEEndoT在心脏肥大的生理作用，并可能确定MEEndoT作为一个新的目标，延缓心脏肥大继发性心力衰竭。

DESCRIPTION (provided by applicant): We have recently described a new biological phenomenon, we have termed mesenchymal-endothelial- transition (MEndoT), where scar forming cells in the heart, exhibit plasticity and adopt endothelial cell like fates after cardiac injury. Fibroblast derived endothelial cells contributed to post injury neovascularization and disruption of MEndoT worsened post injury neovascularization and repair. In contrast, augmentation of MEndoT decreased fibrosis and enhanced cardiac repair, demonstrating the potential of MEndoT as a novel therapeutic target in acute heart injury. In more chronic forms of cardiac injury such as cardiac hypertrophy, increased neovascularization is a critical part of the cardiac compensatory response. Enhanced neovascularization is seen in the initial compensatory phase while regression of vasculature and increased fibrosis are seen in the maladaptive phase prior to the development of heart failure. Disruption of neovascularization accelerates and enhanced neovascularization delays or retards the development of heart failure after cardiac hypertrophy. However whether mesenchymal-endothelial-transition occurs in cardiac hypertrophy and can serve as a therapeutic target for delaying or retarding the development of heart failure is not well understood. In this proposal we provide preliminary evidence that mesenchymal-endothelial transition occurs in cardiac hypertrophy and interrogate the physiological role of MEndoT in cardiac hypertrophy with gain and loss of function approaches. Our experiments will provide novel insight into the physiological role of MEndoT in cardiac hypertrophy and potentially identify MEndoT as a novel target for retarding heart failure secondary to cardiac hypertrophy.