Administrative Core

核心A项目总结 血管疾病和高血压仍然是美国死亡的主要原因。此外，个人 患有代谢综合征的人有更大的后遗症风险，比如心脏病发作。虽然我们知道 多年来关于导致血管疾病的一些因素的重要信息，我们有大量 在理解特定细胞类型如何在血管病变中被募集或激活方面存在差距， 动脉粥样硬化，细胞类型之间的串扰，血管张力的调节，以及这些可能被改变 代谢状况，如肥胖症。这一总体方案项目解决了关键的复杂功能 膜通道，Panx 1，连接许多这些步骤（无论是在生理学和病理学）;我们的研究超过 正在进行的资助期已经表明，这些渠道是“可药物化的”，并且可能是相关的 高血压本PO 1应用的重点是了解Pannexin通道在血管内皮细胞中的作用。 生理学和炎症。项目1将研究Panx 1如何在不同组织环境中调节炎症。 项目2将研究血管平滑肌细胞中Panx 1的表达对高血压的影响。项目3 将在饮食诱导的心脏代谢综合征的背景下解决Panx 1在细胞串扰中的作用。 项目4将使用各种方法来解决泛连接蛋白通道功能的机制细节。的 小鼠核心B将为整体动物研究提供支持，而细胞生理学核心C将提供帮助 分析泛连接蛋白通道在不同细胞类型中的相关性。本行政核心的目的 (Core A）是通过提供科学的管理、赠款和财政援助来协调这一PPG的不同部分。 管理、统计和计算机/数据支持，以及内部和外部科学 咨询会议。

CORE A PROJECT SUMMARY Vascular diseases, and hypertension remains a major cause of mortality in the US. Furthermore, individuals with metabolic syndromes are at an even greater risk of sequelae, such as a heart attack. While we have learned significant information over the years on some of the factors that contribute to vascular disease, we have large gaps in understanding about how specific cell types are recruited or activated in vascular lesions, atherosclerosis, crosstalk between cell types, regulation of vascular tone, and how these might be altered by metabolic conditions such as obesity. This overall program project addresses the intricate functions of key membrane channel, Panx1, which link many of these steps (both in physiology and pathology); Our studies over the ongoing funding period has already suggest that these channels are 'druggable' and can be relevant hypertesion. The focus of this PO1 application is to understand the role of Pannexin channels in vascular physiology and inflammation. Project 1 will study how Panx1 regulates inflammation in different tissue contexts. Project 2 will investigate Panx1 expression in the vascular smooth muscle cells affects hypertension. Project 3 will address the role of Panx1 in cellular crosstalk in the context of diet-induced cadiometabolic syndrome. Project 4 will address the mechanistic details of pannexin channel function using a variety of approaches. The Mouse Core B will provide support for the overall animal studies, while the Cell Physiology Core Cwill help with pannexin channel analysis in different cell types of relevance. The purpose of this Administrative Core (Core A) is to coordinate the different parts of this PPG by providing scientific administration, grant and fiscal management, statistical and computer/data support, and overall coordination of internal and external scientific advisory meetings.