Targeting Gq Signaling in Right Ventricular Hypertrophy

右心室肥大中的靶向 Gq 信号传导

• 批准号: 6626095
• 负责人: CYRUS J PARSA
• 金额: $ 1.82万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626095
• 关键词: G protein; adrenergic receptor; artery stenosis; biological signal transduction; cardiovascular disorder therapy; gene therapy; inhibitor /antagonist; laboratory rabbit; nonhuman therapy evaluation; pathologic process; postdoctoral investigator; pulmonary artery; receptor coupling; ventricular hypertrophy

DESCRIPTION: (provided by applicant): G protein-coupled receptors such as adrenergic receptors (ARs) are critical to heart function. Alpha1-ARs, coupling to the G protein Gq, as well as other Gq-coupled receptors have been implicated in myocardial hypertrophy. Studies in mice have indicated that Gq is a common trigger initiating left ventricular (LV) hypertrophy following pressure overload. The current proposal is centered on right ventricular (RV) hypertrophy and failure, which is of clinical significance (e.g. increased RV afterload via PA stenosis). We are interested in studying the signaling mechanisms involved in RV hypertrophy following an acute and chronic model of PA banding. The proposal examines whether adenoviral-mediated intracoronary gene delivery of GqI to the RV of adult rabbits can attenuate the progression of hypertrophy, dilatation and dysfunction that accompany increased RV afterload. The Central Hypothesis is that Gq is a key figure in the RV hypertrophic response and contributes to the pathogenesis of RV dysfunction and heart failure, and that myocardial gene transfer of a peptide inhibitor of Gq signaling will mitigate the hypertrophic response in the RV following PA banding and improve the acute and chronic biochemical and physiological function of the hypertrophied heart.

描述：（由申请人提供）：G蛋白偶联受体，如 肾上腺素能受体（AR）对心脏功能至关重要。Alpha 1-AR，偶联 与G蛋白Gq以及其他Gq偶联受体有关 心肌肥大在小鼠中的研究表明，Gq是一种常见的 压力后触发启动左心室（LV）肥大 超载。目前的建议是集中在右心室（RV） 具有临床意义的肥大和衰竭（例如RV增加 通过PA狭窄的后负荷）。我们有兴趣研究 在急性和慢性模型后， PA带。该提案研究了腺病毒介导的冠状动脉内 将GqI基因递送到成年兔的RV中可以减弱 伴随RV增加的肥大、扩张和功能障碍 后负荷中心假设认为Gq是RV中的关键人物 肥大反应，并有助于RV功能障碍的发病机制， 心力衰竭与Gq肽抑制剂心肌基因转移 信号传导将减轻PA后RV中的肥大反应 改善急、慢性生化和生理 肥大心脏的功能