ROLE OF HYALURONAN IN CONGENITAL BIRTH DEFECTS AND ATHEROSCLEROSIS

透明质酸在先天性缺陷和动脉粥样硬化中的作用

• 批准号: 7609864
• 负责人: SUNITI MISRA
• 金额: $ 17.63万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609864
• 关键词: 1-Phosphatidylinositol 3-Kinase; Aorta; Atherosclerosis; Computer Retrieval of Information on Scientific Projects Database; Congenital Abnormality; Development; Funding; Grant; Hyaluronan; Inherited; Institution; Maintenance; Mediating; Modeling; Mus; Patent Ductus Arteriosus; Pathway interactions; Phosphoinositide-3-Kinase, Catalytic, Gamma Polypeptide; Rattus; Research; Research Personnel; Resources; Role; Smooth Muscle Myocytes; Source; United States National Institutes of Health; cyclooxygenase 2; enzyme activity; in vivo Model; mouse Smc1l1 protein; mouse Smc1l2 protein

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. Specific Aims: AIM 1: Evaluate the role of HA-CD44 interaction leading to smooth muscle cell (SMC) activation in cellular (normal aortic SMC (ASMC)) and SMC from inherited patent ductus arteriosus (PDA) development in BN/Mcwi rat models. Aim 1A. Determine if increased HA synthesis is sufficient to confer SMC activation in cellular and in vivo models. Aim 1B. Determine if HA-CD44 interaction is necessary for maintenance of SMC activation in cellular and in vivo models. Aim 2: Examine COX-2 mediated effects of HA, and establish that HA-CD44 interaction regulates SMC activation via a pathway involving ErbB2/PI3-kinase (PI3K)/cyclooxygenase-2 (COX-2)in ASMC and DA-SMC/Wistar. Aim 2A. Determine if HA regulates COX-2 enzyme activity in ASMC-HAS2, PDA-SMC-HAS2/ BN transfectants and DA-SMC/Wister. Aim 2B. Determine whether COX-2 alone mediates HA-induced effects on SMC activation in the above HAS2 transfected and primary cultures as in ¿ Aim 2A. Aim 3: Determine the mechanism of HA-COX-2 pathway for SMC activation in SMCs from developing DA versus aorta of LDR-/- versus WT mice. Aim 3A. Determine if HA regulates COX-2 enzyme activity in SMCs from aorta of LDR-/- versus WT mice. Aim 3B. Determine whether COX-2 alone mediates HA-induced effects on SMC activation in the above primary cultures as in ¿ Aim 3A. Aim 3C. Determine whether HA-COX-2 pathway mediates intimal thickening via SMC activation in intact explants from the above primary cultures as in ¿ Aim 3A.

该副本是使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，这是调查员的机构。 具体目的： AIM 1：评估HA-CD44相互作用在BN/MCWI大鼠模型中从遗传专利导管（PDA）发育中引起细胞（正常主动脉SMC（ASMC））和SMC中平滑肌细胞（SMC）激活的作用。 目标1a。确定增加的HA合成是否足以在细胞和体内模型中赋予SMC激活。 目标1B。确定HA-CD44相互作用对于维持细胞和体内模型中的SMC激活是否需要。 AIM 2：检查COX-2介导的HA效应，并确定HA-CD44相互作用通过ASMC和DA-SMC/Wistar中的涉及ERBB2/PI3-激酶（PI3K）/环氧酶-2（COX-2）的途径调节SMC激活。 目标2a。确定HA是否调节ASMC-HAS2，PDA-SMC-HAS2/ BN转染剂和DA-SMC/ Wister中的COX-2酶活性。 目标2B。确定单独的COX-2是否介导HA诱导的对上述has2翻译和原代培养物中SMC激活的影响，例如AIM 2A中。 AIM 3：确定从发育中的DA与LDR - / - 与WT小鼠的主动脉相对于主动脉的SMC激活中HA-COX-2途径的机制。 目标3a。确定HA是否调节来自LDR - / - 与WT小鼠主动脉的SMC中的COX-2酶活性。 目标3B。确定单独的COX-2是否介导HA诱导的对上述原发性培养物中SMC激活的影响，例如AIM 3A。 AIM 3C。确定HA-COX-2途径是否像AIM 3A中的上述原发性培养物中的完整培养基中的SMC激活中介导了内膜增厚。