Endothelial Biology
Endothelial Biology
批准号:
7226088
负责人:
ROBERT P HEBBEL
金额:
$38.22万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-12-01 至 2011-11-30
关键词:
Abnormal Endothelial CellAffectBiologicalBiologyBlood ClotBlood Coagulation DisordersBlood VesselsBlood coagulationCoagulation ProcessEnd PointEndothelial CellsEndotheliumExhibitsHeterogeneityHumanHuman BiologyHypoxiaIndividualInflammationLocationLungMediatingMedicalMolecularMonitorMusNF-kappa BOrganPersonal SatisfactionPhenotypePhysiologyPlayPulmonary veinsReperfusion InjuryRoleSickle CellSickle Cell AnemiaSideStressStrokeTestingThromboplastinThrombosisVeinsinterestmonocytemouse modelnovelnovel therapeuticsperipheral bloodpreventsickling
中文摘要
这个项目将进一步发展镰状病作为再灌注损伤生理学的一个例子
重点研究肺静脉组织因子异常表达的内皮激活终点
恩多塞。这种关注是合理的,因为:[a]它将扩展对TF生物学的理解;[B]它
包括内皮细胞活化的稳健终点指标;并且[c]其具有很大的潜在重要性
镰状病,其中受影响的个体具有凝血病和血栓形成。我们将研究5
具体目标。[1]确定镰状小鼠的不同之处,这导致它们-而不是正常小鼠-
发展内皮TF表达。我们的主要假设是炎症起主要作用,
这是由外周血单核细胞介导的,并由来自内皮eNOS的NO调节。
[2]删除。[3]评估内皮TF表达的位置、功能和相关性。我们的关键
假设:内皮TF是功能性的,在内皮细胞的腔侧表达;
并且TF表达的抑制(在小鼠和人中)将通过凝血的减少而被消除
激活状态[4]在分子和整体小鼠水平上确定内皮TF的潜在机制
表达和抑制。我们的主要假设是,虽然NF κ B对内皮TF是允许的,
在镰状小鼠模型中表达,Egr-1是必需的。[5]研究为什么在血管内皮细胞中存在内皮异质性,
TF表达。内皮TF表达局限于肺,在该器官内局限于静脉,
只有一些静脉。理解这个非常有趣的内皮细胞表型的例子的原因
异质性不仅具有普遍的生物学意义,而且具有一定的医学重要性。给你钥匙
假设TF阳性静脉表现出这种表型,是因为之前的低氧应激大于
TF阴性静脉我们将研究镰状细胞小鼠,以确定它们为什么异常
易缺氧并表达组织因子,触发血液凝固。这些的重要性
这些研究很好地帮助我们开发了一种新的治疗镰状病的方法,
影响孩子的问题。
英文摘要
This Project will further develop the theme of sickle disease as an example of reperfusion injury physiology
and focus on the endothelial activation endpoint of abnormal expression of tissue factor by pulmonary vein
ndothelium. This focus is justified because: [a] it will extend the understanding of TF biology; [b] it
comprises a robust endpoint indicator of endothelial cell activation; and [c] it is of great potential importance
n sickle disease, in which affected individuals have a coagulopathy and thromboses. We will examine 5
Specific Aims. [1] Identify what is different about sickle mice, that leads them - but not normal mice - to
develop endothelial TF expression. Our Key Hypotheses are that inflammation plays the primary role, and
that this is mediated by peripheral blood monocytes, and modulated by NO from endothelial eNOS.
[2]deleted. [3] Assess the location, functionality, and relevance of endothelial TF expression. Our Key
Hypotheses are: that endothelial TF is functional and expressed on the lumen side of the endothelial cell;
and that inhibition of TF expression (in mouse and human) will be paralleled by diminution in coagulation
activation state. [4] Identify, at molecular and whole mouse levels, the mechanism underlying endothelial TF
expression and inhibition. Our Key Hypotheses is that while NFKB is permissive for endothelial TF
expression in sickle mouse model, Egr-1 is essential. [5] Examine why there is endothelial heterogeneity in
TF expression. Endothelial TF expression is confined to the lungs, and within this organ to the veins, and
only some veins. Understanding the reason for this very interesting example of endothelial phenotype
heterogeneity is not only of general biological interest, but also of some medical importance. Here, our Key
Hypotheses is that the TF positive veins exhibit this phenotype because of greater prior hypoxic stress than
the TF negative veins. LAY SUMMARY: We will study sickle cell mice to determine why they are abnormally
susceptible to hypoxia and express tissue factor, the trigger of blood clotting. The importance of these
studies is that they well help us develop a novel therapy for sickle disease that will prevent the large stroke
problem in affected kids.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Non-viral gene therapy for sickle cell anemia
-
批准号:8293156
-
项目类别:
-
资助金额:$63.31万
-
财政年份:2009
-
负责人:ROBERT P HEBBEL
-
依托单位:
Non-viral gene therapy for sickle cell anemia
-
批准号:8065383
-
项目类别:
-
资助金额:$69.22万
-
财政年份:2009
-
负责人:ROBERT P HEBBEL
-
依托单位:
Non-viral gene therapy for sickle cell anemia
-
批准号:7900987
-
项目类别:
-
资助金额:$37.74万
-
财政年份:2009
-
负责人:ROBERT P HEBBEL
-
依托单位:
Non-viral gene therapy for sickle cell anemia
-
批准号:7686636
-
项目类别:
-
资助金额:$37.75万
-
财政年份:2009
-
负责人:ROBERT P HEBBEL
-
依托单位:
Transgenic Mouse
-
批准号:7226098
-
项目类别:
-
资助金额:$54.59万
-
财政年份:2006
-
负责人:ROBERT P HEBBEL
-
依托单位:
Admininstration Core
-
批准号:7226094
-
项目类别:
-
资助金额:$8.6万
-
财政年份:2006
-
负责人:ROBERT P HEBBEL
-
依托单位:
GENETIC HETEROGENEITY IN ENDOTHELIAL GENE EXPRESSION
-
批准号:6946584
-
项目类别:
-
资助金额:$53.85万
-
财政年份:2004
-
负责人:ROBERT P HEBBEL
-
依托单位:
BOEC in Biology
-
批准号:6746013
-
项目类别:
-
资助金额:$29.7万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
CORE--TRANSGENIC ANIMALS
-
批准号:6581195
-
项目类别:
-
资助金额:$15.09万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
BOEC in Biology
-
批准号:6609692
-
项目类别:
-
资助金额:$29.7万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
BOEC in Biology
-
批准号:6531229
-
项目类别:
-
资助金额:$29.7万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
BOEC in Biology
-
批准号:6895834
-
项目类别:
-
资助金额:$29.7万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
REPERFUSION INJURY
-
批准号:6581192
-
项目类别:
-
资助金额:$15.09万
-
财政年份:2002
-
负责人:ROBERT P HEBBEL
-
依托单位:
ENDOTHELIAL CELL OUTGROWTH FROM BLOOD
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批准号:6042201
-
项目类别:
-
资助金额:$10.19万
-
财政年份:2000
-
负责人:ROBERT P HEBBEL
-
依托单位:
ENDOTHELIAL CELL OUTGROWTH FROM BLOOD
-
批准号:6351574
-
项目类别:
-
资助金额:$10.19万
-
财政年份:2000
-
负责人:ROBERT P HEBBEL
-
依托单位:
DEVELOPMENTAL HEMATO-ENDOTHELIAL BIOLOGY OF P1H12
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批准号:2900364
-
项目类别:
-
资助金额:$33.44万
-
财政年份:1999
-
负责人:ROBERT P HEBBEL
-
依托单位:
DEVELOPMENTAL HEMATO-ENDOTHELIAL BIOLOGY OF P1H12
-
批准号:6381628
-
项目类别:
-
资助金额:$38.47万
-
财政年份:1999
-
负责人:ROBERT P HEBBEL
-
依托单位:
DEVELOPMENTAL HEMATO-ENDOTHELIAL BIOLOGY OF P1H12
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批准号:6422665
-
项目类别:
-
资助金额:$4.11万
-
财政年份:1999
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负责人:ROBERT P HEBBEL
-
依托单位:
REPERFUSION INJURY
-
批准号:6202437
-
项目类别:
-
资助金额:$15.09万
-
财政年份:1999
-
负责人:ROBERT P HEBBEL
-
依托单位:
CORE--TRANSGENIC ANIMALS
-
批准号:6202440
-
项目类别:
-
资助金额:$15.09万
-
财政年份:1999
-
负责人:ROBERT P HEBBEL
-
依托单位:
海外基金