Prevention of Vein Graft Failure

预防静脉移植失败

• 批准号: 10089464
• 负责人: Colleen M Brophy
• 金额: $ 57.37万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089464
• 关键词: Adenosine Triphosphate; Angioplasty; Back; Biology; Biomechanics; Blood Vessels; Bypass; Cardiovascular Diseases; Caspase; Cells; Cessation of life; Cleaved cell; Clinical; Coronary; Data; Development; Dyes; Endothelium; Event; Exposure to; Extracellular Space; Family suidae; Funding; Harvest; Human; Hyperplasia; Impairment; Inflammation; Inflammatory Response; Injury; Interleukin-1 beta; Investigation; Kidney; Lung; MAP Kinase Gene; MAPKAPK2 gene; Mediator of activation protein; Modality; Modeling; Molecular; Nervous system structure; Operative Surgical Procedures; Oryctolagus cuniculus; Pathologic; Pathway interactions; Patients; Peptides; Peripheral; Preparation; Prevention; Process; Production; Property; Purinoceptor; RNA; Relaxation; Role; SB 203580; Saphenous Vein; Stretching; Surgical Injuries; Therapeutic; Thrombosis; Traction; Transplantation; Trauma; Vascular Graft; Vasospasm; Vein graft; Veins; Water; Work; arginase; cytokine; endothelial dysfunction; external jugular vein; extracellular; graft failure; haptics; implantation; inhibitor/antagonist; insight; novel strategies; p38 Mitogen Activated Protein Kinase; preservation; prevent; public health relevance; receptor; response; response to injury; small molecule inhibitor; technique development; vascular injury

Project Summary/Abstract While the “response to injury” associated with pathologic vascular damage has been described as the initiator of vascular graft failure, there is very little information about the molecular mediator of this process. We propose that ATP released during surgical harvest of human saphenous vein activates purinergic receptors (P2X7R) leading to a cascade of events that promulgate and potentiate the response to injury. Understanding the role of ATP and P2X7R pathway activation in response to vascular injury will lead to specific modalities to prevent and treat the injury that occurs during surgical harvest of HSV. This work will also provide new insights in vascular biology with potential extensions to other applications such as vascular injury during angioplasty, transplantation, and trauma.

项目概要/摘要 虽然与病理性血管损伤相关的“对损伤的反应”已被证实 被描述为血管移植失败的始作俑者，但关于它的信息很少 我们认为手术过程中会释放 ATP。 人类隐静脉的收获会激活嘌呤能受体（P2X7R），从而导致 一系列事件的传播和加强对伤害的反应。 了解 ATP 和 P2X7R 通路激活在血管反应中的作用 伤害将导致采取特定的方式来预防和治疗期间发生的伤害 这项工作也将为血管生物学提供新的见解。 具有潜在的扩展到其他应用的潜力，例如血管损伤 血管成形术、移植和创伤。

项目成果

The Cell Permeant Phosphopetpide mimetic of VASP Alleviates Motor Function Deficits After Experimental Subarachnoid Hemorrhage.

VASP 的细胞渗透性磷酸肽模拟物可减轻实验性蛛网膜下腔出血后的运动功能缺陷。

• 发表时间: 2024-01-12
• 作者: Morelli, Madeleine;Adcock, Jamie;Yim, Tsz Wing;Rook, Jerri;Mocco, J;Brophy, Colleen;Cheung
• 通讯作者: Cheung

Enhanced skin penetration of P20 phosphopeptide using protein transduction domains.

使用蛋白质转导域增强 P20 磷酸肽的皮肤渗透性。

• DOI: 10.1016/j.ejpb.2007.09.019
• 发表时间: 2008-02-01
• 期刊: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
• 作者: L. B. Lopes;Elizabeth Furnish;P. Komalavilas;Br;on L. Seal;on;A. Panitch;M. Bentley;C. Brophy
• 通讯作者: C. Brophy

Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation and Actin Polymerization in Human Saphenous Vein.

罂粟碱通过调节人隐静脉中肌球蛋白轻链磷酸化和肌动蛋白聚合来预防血管痉挛。

• 发表时间: 2016
• 影响因子: 3.7
• 作者: Hocking, Kyle M;Putumbaka, Gowthami;Wise, Eric S;Cheung;Brophy, Colleen M;Komalavilas, Padmini
• 通讯作者: Komalavilas, Padmini

Vascular surgical stretch injury leads to activation of P2X7 receptors and impaired endothelial function.

血管手术牵拉损伤导致 P2X7 受体激活和内皮功能受损。

• 发表时间: 2017
• 影响因子: 3.7
• 作者: Komalavilas, Padmini;Luo, Weifeng;Guth, Christy M;Jolayemi, Olukemi;Bartelson, Rachel I;Cheung;Brophy, Colleen M
• 通讯作者: Brophy, Colleen M

Blocking P2X7 receptor with AZ 10606120 exacerbates vascular hyperpermeability and inflammation in murine polymicrobial sepsis.

使用 AZ 10606120 阻断 P2X7 受体会加剧小鼠多种微生物败血症的血管通透性过高和炎症。

• 发表时间: 2022-06
• 影响因子: 2.5
• 作者: Meegan, Jamie E;Komalavilas, Padmini;Cheung;Yim, Tsz Wing;Putz, Nathan D;Jesse, Jordan J;Smith, Kyle D;Sidorova, Tatiana N;Lee, Han Noo Ri;Tomasek, Toria;Shaver, Ciara M;Ware, Lorraine B;Brophy, Colleen M;Bastarache, Julie A
• 通讯作者: Bastarache, Julie A