Mechanisms of Collateral Arteriogenesis in Ischemia

缺血时侧支动脉生成的机制

• 批准号: 7208056
• 负责人: DAN CHALOTHORN
• 金额: $ 5.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-18 至 2008-03-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208056
• 关键词: A Mouse; Adult; Anastomosis - action; Angiography; Apoptosis; Arteries; Atherosclerosis; Biology; Blood Vessels; Blood capillaries; Blood flow; CCL2 gene; Cardiac; Cell Communication; Cells; Cerebrum; Chronic; Complex; Data; Dependence; Deposition; Development; Diabetes Mellitus; Diagnostic radiologic examination; Disease; Embryo; Embryonic Development; Endothelial Cells; Epithelial; Erinaceidae; Exhibits; Fibroblasts; Future; Goals; Hour; Hypertension; Image; Immigration; Immunoblotting; Immunohistochemistry; Impairment; In Situ Hybridization; Injury; Intercellular adhesion molecule 1; Invasive; Investigation; Ischemia; Knowledge; LacZ Genes; Lasers; Leukocytes; Ligation; Limb structure; Literature; Measurement; Measures; Mediating; Mesenchymal; Methodology; Methods; Microspheres; Modeling; Mouse Strains; Mus; Muscle Fibers; Muscular Atrophy; Pathway interactions; Patients; Pattern; Perfusion; Pericytes; Peripheral; Permeability; Polymerase Chain Reaction; Process; Protein Isoforms; Purpose; Recovery; Regulation; Reporter; Resolution; Risk; Role; Signal Transduction; Smooth Muscle; Sonic Hedgehog Pathway; Stromal Cells; Testing; Time; Tissues; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Week; analog; angiogenesis; arteriole; artery occlusion; body system; capillary; concept; day; density; femoral artery; genetic strain; improved; nectin; neutralizing antibody; notch protein; prevent; receptor; research study; response

DESCRIPTION (provided by applicant): The purpose of this project is to improve our understanding of arteriogenesis in ischemia. This process, consisting of outward remodeling of pre-existing arteriole anastomoses and formation of new or "neo-collaterals", is not well understood. Moreover, many patients with ischemic disease show a deficit in collateral development. A mouse strain with a severe deficiency in recovery of perfusion after artery ligation has been identified, but the reasons for the impairment are unknown. Aim I will use new methods we have developed for imaging arteriogenesis, will introduce a new strategy for study of neo-collateral formation, and will test the hypothesis that formation of neo-collaterals is defective in the strain. There is evidence that the morphogenic pathway, Sonic hedgehog-notch, which mediates early vascular development, may be reactivated in adults during injury and/or remodeling. A role for this pathway in arteriogenesis has not been studied. Our preliminary data suggest Shh signaling is important in collateral maturation. Therefore, Aim II will examine the hypothesis that Shh-notch signaling contributes to pre-existing collateral maturation and neo-collateral formation, and that it is defective in the impaired strain.

描述（由申请人提供）：本项目的目的是提高我们对缺血动脉发生的认识。这一过程包括原有小动脉吻合处的向外重塑和新侧支的形成，目前尚不清楚。此外，许多缺血性疾病患者表现出侧枝发育的缺陷。已发现一种小鼠品系在动脉结扎后灌注恢复严重不足，但其原因尚不清楚。目的：我将使用我们开发的动脉发生成像的新方法，将引入新侧枝形成研究的新策略，并将测试新侧枝形成在菌株中有缺陷的假设。有证据表明，在成人损伤和/或重塑过程中，介导早期血管发育的形态发生通路Sonic hedgehog-notch可能被重新激活。该途径在动脉发生中的作用尚未被研究。我们的初步数据表明Shh信号在侧枝成熟中很重要。因此，Aim II将检验sh -notch信号有助于预先存在的侧枝成熟和新侧枝形成的假设，并且它在受损菌株中是缺陷的。

项目成果

Arginase blockade lessens endothelial dysfunction after thrombosis.

精氨酸酶阻断可减轻血栓形成后的内皮功能障碍。

• DOI: 10.1016/j.jvs.2008.02.030
• 发表时间: 2008
• 期刊: Journal of vascular surgery
• 影响因子: 4.3
• 作者: Lewis,Chandani;Zhu,Weifei;Pavkov,MirceaL;Kinney,CorttrellM;Dicorleto,PaulE;Kashyap,VikramS
• 通讯作者: Kashyap,VikramS