REGULATION OF VASCULAR REMODELING IN ADULT MYOCARDIUM BY THYROID HORMONES

甲状腺激素对成人心肌血管重塑的调节

• 批准号: 7959740
• 负责人: Daguang Wang
• 金额: $ 20.34万
• 依托单位: SANFORD RESEARCH/USD
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959740
• 关键词: Adult; Animals; Blood Vessels; Blood flow; Cardiac; Cardiovascular system; Computer Retrieval of Information on Scientific Projects Database; Coronary Vessels; Evolution; Funding; Goals; Grant; Growth; Heart; Heart Hypertrophy; Hypertrophy; In Vitro; Institution; Link; Molecular; Muscle Cells; Myocardium; Pathologic; Pathway interactions; Phenotype; Physiological; Play; Process; Regulation; Research; Research Personnel; Resources; Role; Signal Pathway; Signal Transduction; Source; Stem cells; Testing; Thyroid Hormones; United States National Institutes of Health; Vascular Diseases; Vascular remodeling; angiogenesis; density

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to study the cellular and molecular mechanisms of vascular growth in adult hearts. Proliferation of microcirculatory vessels parallels myocyte hypertrophy during normal growth and maturation. Many studies, however, have demonstrated that impaired vascular growth and vascular disease play a major role in pathologic cardiac hypertrophy. This may involve reduced density of coronary vessels and impaired regulation of blood flow. Recent studies have provided more mechanistic information about the role of impaired vascular growth in the evolution of pathologic cardiac hypertrophy. Indeed, it appears that blocking vascular growth during physiological cardiac hypertrophy results in conversion to a pathologic phenotype. Thyroid hormones (THs) are known to stimulate vascular growth and activate the Akt pathway. To this point, however, cardiac vascular growth has not been mechanistically linked to Akt pathway. ____________________ In this study, we will test the hypothesis that TH's promote angiogenesis via an Akt signaling pathway in adult myocardium and this process is accompanied by mobilization of endothelial progenitor cells. To test this hypothesis Aim 1 will extensively characterize the cellular features of T3-induced angiogenesis in adult heart and determine the role of Akt signaling. Aim 2 will use the animals from Aim 1 to investigate the effect of T3 on the mobilization of endothelial progenitor cells. Aim 3 will explore the role of the PI3K-Akt-HIF-1 signaling pathway in TH induced vascular remodeling and vessel integrity during the angiogenic process in vitro.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究的目的是研究成人心脏血管生长的细胞和分子机制。在正常生长和成熟过程中，微循环血管的增殖与心肌肥大相似。然而，许多研究表明，血管生长和血管疾病受损在病理心脏肥大中起主要作用。这可能涉及冠状动脉血管的密度降低和血流调节受损。最近的研究提供了有关血管生长受损在病理心脏肥大进化中的作用的更多机制信息。 确实，似乎阻断生理心脏肥大过程中血管生长导致转化为病理表型。已知甲状腺激素（THS）刺激血管生长并激活AKT途径。然而，至此，心脏血管生长尚未与AKT途径相关。 ________________________ 在这项研究中，我们将检验以下假设：TH通过成人心肌中的AKT信号通路促进血管生成，并且该过程伴随着动员内皮祖细胞的动员。为了检验该假设，目标1将广泛地表征T3诱导的成人心脏血管生成的细胞特征，并确定Akt信号的作用。 AIM 2将使用AIM 1的动物研究T3对动员内皮祖细胞的影响。 AIM 3将探讨PI3K-AKT-HIF-1信号通路在体外血管生成过程中诱导的血管重塑和血管完整性中的作用。