Natriuretic Peptide Receptor and Cardiomyocyte Biology

项目主任/主要研究者（最后，第一，中间）：伯内特，约翰。C. Jr. 项目1 标题：利钠肽受体与心肌细胞生物学 项目描述：该提案旨在开发一种新的、心脏特异性的、可翻译的 基于心脏特异性利钠肽过表达的舒张性心力衰竭（DHF）治疗 通过腺相关病毒（AAV）基因递送，将鸟苷酸环化酶A（GCA）与受体结合。我们将优化 啮齿动物心脏中GCA过表达，证明通过基因递送恢复心脏GCA防止了 GCA缺陷小鼠（全身性（GCA）缺陷小鼠和心脏特异性（CS-）缺陷小鼠）心力衰竭 GCAnuii）切除GCA基因）并逆转具有已建立DHF的野生型小鼠的心力衰竭。这些 研究为今后在大型哺乳动物和人类DHF中的翻译奠定了基础。 项目负责人：Margaret M.雷德菲尔德医学教授 其他

Program Director/Principal Investigator (Last, First, Middle): Burnett, John. C. Jr. PROJECT 1 Title: Natriuretic Peptide Receptor and Cardiomyocyte Biology Project Descripfion: This proposal seeks to develop a novel, cardiac specific and ulfimately translatable therapy for diastolic heart failure (DHF) based on the cardiac specific over-expression of the natriuretic pepfide receptor (guanylyl cyclase A (GCA)) via adeno-associated viral (AAV) gene delivery. We will optimize overexpression of GCA in rodent heart, demonstrate that restoration of cardiac GCA via gene delivery prevents heart failure in GCA deficient mice (mice witli systemic (GCA"uit) and mice witti cardiac specific (CS- GCAnuii) ablation ofthe GCA gene) and reverses heart failure in wild type mice with established DHF. These studies lay the foundation for translation to large mammal and human DHF in future studies. Project Leader: Margaret M. Redfield. MD; Professor of Medicine Other