The role of HIF-1 and its regulators p53 and Smyd2 in right ventricular hypertrophy and failure (B04)

HIF-1 及其调节因子 p53 和 Smyd2 在右心室肥厚和衰竭中的作用 (B04)

• 批准号: 314336575
• 金额: --
• 依托单位: Biomedizinisches Forschungszentrum Seltersberg (BFS)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/314336575?language=en
• 关键词: role; HIF; its; regulators; p53

This project aims to investigate the role and interplay of Hypoxia Inducible Factor-1 (HIF-1), the tumor suppressor p53, the Bone Morphogenic Protein Receptor type II (BMPR2) and the methyltransferase Smyd2 in cardiac endothelial cells (cECs) and cardiomyocytes (CMs) by gain- and loss-of-function experiments. The impact of cell (cEC, CM)-specific overexpression and knockdown of HIF-1α, p53, Bmpr2 and Smyd2 in early adaptive and late maladaptive RV remodeling will be analyzed in mice undergoing pulmonary artery banding surgery. The ultimate goal is to understand the role of these proteins in RV remodeling aiming to develop novel treatment strategies.

本项目旨在通过功能获得和功能丧失实验研究缺氧诱导因子-1（HIF-1）、肿瘤抑制因子p53、骨形态发生蛋白受体II型（BMPR 2）和甲基转移酶Smyd 2在心脏内皮细胞（cECs）和心肌细胞（CMs）中的作用和相互作用。将在接受肺动脉结扎手术的小鼠中分析细胞（cEC，CM）特异性过表达和HIF-1α、p53、Bmpr 2和Smyd 2敲低对早期适应性和晚期适应不良RV重塑的影响。最终目标是了解这些蛋白在RV重塑中的作用，旨在开发新的治疗策略。