Hemodynamics and hepatic remodeling
血流动力学和肝脏重塑
基本信息
- 批准号:9542958
- 负责人:
- 金额:$ 37.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-05-05 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AreaArteriesBiologyBlood VesselsBlood flowBuffersCellsCirrhosisComplicationDataDefectDevelopmentEndothelial CellsExperimental ModelsFibrosisGoalsHepaticHepatic arteryImmuneInfiltrationKDR geneLigandsLigationLightLiverLiver CirrhosisLiver FibrosisMediatingMicroRNAsMusMutationMyofibroblastOperative Surgical ProceduresOrganPartial HepatectomyPharmacologyPortal HypertensionPortal vein structureRattusResearchRoleSignal TransductionSiteSourceSpleenSplenectomyStructureSurgical ModelsT-LymphocyteTestingThrombosisTransmembrane DomainTransplantationVascular Cell Adhesion Molecule-1VasodilationVenousarterial remodelingcadherin 5chronic liver diseaseexosomehemodynamicshepatic veinliver transplantationmacrophagemechanotransductionnovelrecruitresponse
项目摘要
SUMMARY
The goal of this study is to understand the effects of hemodynamic changes on liver structure and
function with a focus on portal hypertension. Portal hypertension is a major complication of chronic liver
disease. Liver cirrhosis is its most common cause, but it develops in non-cirrhotic conditions as well. In portal
hypertension, portal venous flow decreases, while hepatic arterial (HA) flow increases because of a
combination of a hepatic arterial buffer response and vasodilation of splanchnic arteries. How these changes
influence liver structure and function is largely unknown.
Our preliminary data show that rats with partial portal vein ligation (PPVL; a surgical model of portal
hypertension) develop portal tract fibrosis. PPVL partially occludes the portal vein at a pre-hepatic site and
leads to portal hypertension and increased HA-flow. Rats with PPVL also showed increased infiltration of
macrophages and T-cells in portal tracts. Further, increased blood flow is known to cause remodeling of
arterial walls, mediated by transient accumulation and activation of perivascular macrophages and T-cells.
Therefore, we hypothesize that increased HA-flow in portal hypertension facilitates portal tract fibrosis by
recruiting macrophages and T-cells through signals that are mediated by mechano-transduction. Liver
remodeling through enhanced HA-flow could also be a second hit that amplifies liver fibrosis/cirrhosis. Further,
we hypothesize that the spleen is an important source of the infiltrating immune cells.
To test these hypotheses, we propose to examine the following three aims: 1) Determine the role of
HA-flow in the development of portal tract fibrosis and the significance of flow-induced portal tract fibrosis in the
progression of liver fibrosis/cirrhosis, 2) Determine the mechanism by which increased HA-flow causes
immune cell infiltration and portal tract fibrosis, and 3) Determine the mechanism by which immune cells
regulate portal tract fibrosis.
总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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YASUKO IWAKIRI其他文献
YASUKO IWAKIRI的其他文献
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{{ truncateString('YASUKO IWAKIRI', 18)}}的其他基金
Hepatic lymphatics in alcohol-associated liver disease
酒精相关性肝病中的肝淋巴管
- 批准号:
10824029 - 财政年份:2023
- 资助金额:
$ 37.69万 - 项目类别:
Endotheliopathy and liver injury in COVID-19
COVID-19 中的内皮病和肝损伤
- 批准号:
10468220 - 财政年份:2021
- 资助金额:
$ 37.69万 - 项目类别:
Endotheliopathy and liver injury in COVID-19
COVID-19 中的内皮病和肝损伤
- 批准号:
10662455 - 财政年份:2021
- 资助金额:
$ 37.69万 - 项目类别:
Endotheliopathy and liver injury in COVID-19
COVID-19 中的内皮病和肝损伤
- 批准号:
10319358 - 财政年份:2021
- 资助金额:
$ 37.69万 - 项目类别:
The role of Kupffer cells in alcohol-induced liver disease
库普弗细胞在酒精性肝病中的作用
- 批准号:
9761401 - 财政年份:2017
- 资助金额:
$ 37.69万 - 项目类别:
Mechanisms of Alcohol-Induced Hepatic Osteodystrophy
酒精性肝性骨营养不良的机制
- 批准号:
8969937 - 财政年份:2016
- 资助金额:
$ 37.69万 - 项目类别:
Mechanisms of Alcohol-Induced Hepatic Osteodystrophy
酒精性肝性骨营养不良的机制
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9326892 - 财政年份:2016
- 资助金额:
$ 37.69万 - 项目类别:
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