Disease-specific risk factors for thrombosis following vascular interventions
Disease-specific risk factors for thrombosis following vascular interventions
批准号:
10733113
负责人:
Vipul C Chitalia
金额:
$69.41万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-01 至 2027-07-31
关键词:
AddressAffectAmericanAngioplastyAnimal ModelArteriesAryl Hydrocarbon ReceptorBiogenesisBiological MarkersBloodBlood VesselsCardiovascular DiseasesCarotid Artery ThrombosisCessation of lifeChronic Kidney FailureClinicalClinical TrialsComplicationCoronary arteryDataDialysis procedureDiseaseEnzymesEventExtracellular MatrixFrequenciesGene SilencingGenerationsGeneticHemostatic functionHumanITIMIndicanInflammationInflammatoryInterventionInvestigationKnockout MiceKynurenineLigationMediatingMediatorModelingMolecularMusOperative Surgical ProceduresOrganPDGFRB genePathologyPathway interactionsPatientsPersonsPhosphorylationPlasminogen Activator Inhibitor 1Platelet-Derived Growth Factor beta ReceptorProceduresProductionProtein-Lysine 6-OxidaseProteinsRegulationRenal functionResearchRiskRisk FactorsSignal TransductionThromboplastinThrombosisTimeToxic effectToxinTryptophanTryptophan 2,3 DioxygenaseTyrosineUp-RegulationUremiaVeinsVenous ThrombosisWorkburden of illnesscostcytokineexperiencehigh riskhuman modelinhibitorinnovationknockout genemortalitymouse modelnew therapeutic targetnovelpharmacologicpost interventionsolutetherapeutic targetthrombogenesisthrombotictrendubiquitin-protein ligasevascular injury
中文摘要
摘要
英文摘要
Abstract
Vasculo-thrombosis and altered hemostasis are associated with several organ pathologies, the disease-
specific mediators of which remain poorly understood. This aspect is particularly relevant in chronic kidney
disease (CKD), which affects 30 million Americans. Patients with CKD suffer from high cardiovascular disease
burden, making CKD patients in need of frequent vascular interventions, such as endovascular procedures or
vascular surgery. A CKD milieu (uremia) is a strong and independent risk factor for thrombosis after such
procedures. Given the upward trend of CKD in general, and high frequency of interventional procedures in them,
investigating such post-interventional complications and means to control them is a worthy pursuit.
CKD is characterized by retention of a host of uremic solutes. Although studies in humans and animal
models implicate the uremic solutes indoxyl sulfate and kynurenine as CKD-specific risk factors and are,
therefore, perceived as tantalizing therapeutic targets for cardiovascular disease, their exact mechanism of
actions remains poorly understood. This underpinning will be addressed in the current proposal. Our work in
recent years elucidated prothrombotic propensities of indolic uremic toxins, partially mediating their toxicity
through upregulation of tissue factor in vSMCs. Here, building on new data, we propose an integrative approach
to study newly identified converging pathways that augment thrombosis in CKD, consisting of Indoleamine 2,3-
dioxygenase-1 (IDO1), a key enzyme in kynurenine production, and lysyl oxidase (LOX), a key enzyme regulator
of extracellular matrix remodeling and thrombosis. Aim 1 examines a novel regulation of IDO1 level and activity
by indoxyl sulfate and/or kynurenine, and its contribution to uremic thrombosis, using genetic and
pharmacological manipulation of IDO1 in a CKD mouse model. Aim 2 builds on our new findings suggesting
LOX expression as a target of indoxyl sulfate and kynurenine, thereby contributing to uremia-induced vasculo-
thrombosis. This aim employs molecular and gene knockout approaches to understand the control of LOX
biogenesis in VSMCs in a uremic milieu, and its contribution to thrombosis in context of CKD. Both aims of
research will utilize arterial and venous thrombosis models in CKD mice. Successful completion of this proposal
will define CKD-associated common mediators of thrombosis. Along with mechanistic advances, our proposed
investigations might pave ways to repurposing advanced clinical compounds for the management of vascular
occlusion in CKD patients.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Frequency domain shortwave infrared spectroscopy (FD-SWIRS) for volume status monitoring during hemodialysis in end stage kidney disease
-
批准号:10432546
-
项目类别:
-
资助金额:$22.4万
-
财政年份:2022
-
负责人:Vipul C Chitalia
-
依托单位:
Frequency domain shortwave infrared spectroscopy (FD-SWIRS) for volume status monitoring during hemodialysis in end stage kidney disease
-
批准号:10580084
-
项目类别:
-
资助金额:$25.41万
-
财政年份:2022
-
负责人:Vipul C Chitalia
-
依托单位:
The Boston University Kidney and Medical Engineering Program (BU-KIDMEP)
-
批准号:10600006
-
项目类别:
-
资助金额:$12.57万
-
财政年份:2021
-
负责人:Vipul C Chitalia
-
依托单位:
The Boston University Kidney and Medical Engineering Program (BU-KIDMEP)
-
批准号:10373102
-
项目类别:
-
资助金额:$12.8万
-
财政年份:2021
-
负责人:Vipul C Chitalia
-
依托单位:
The Boston University Kidney and Medical Engineering Program (BU-KIDMEP)
-
批准号:10229883
-
项目类别:
-
资助金额:$13.6万
-
财政年份:2021
-
负责人:Vipul C Chitalia
-
依托单位:
Role of intravascular ultrasound in Central Venous Stenosis in ESRD patients
-
批准号:10190925
-
项目类别:
-
资助金额:$26.39万
-
财政年份:2020
-
负责人:Vipul C Chitalia
-
依托单位:
Role of intravascular ultrasound in Central Venous Stenosis in ESRD patients
-
批准号:9896231
-
项目类别:
-
资助金额:$23.9万
-
财政年份:2020
-
负责人:Vipul C Chitalia
-
依托单位:
Thrombotic complication of uremia: role of prothrombotic uremic solutes
-
批准号:9244842
-
项目类别:
-
资助金额:$43.5万
-
财政年份:2016
-
负责人:Vipul C Chitalia
-
依托单位:
Role of c-Cbl in Colon cancer
-
批准号:9477471
-
项目类别:
-
资助金额:$36.11万
-
财政年份:2014
-
负责人:Vipul C Chitalia
-
依托单位:
Role of c-Cbl in Colon cancer
-
批准号:9062392
-
项目类别:
-
资助金额:$36.11万
-
财政年份:2014
-
负责人:Vipul C Chitalia
-
依托单位:
Role of Wnt signaling in uremia-induced entothelial dysfunction
-
批准号:8109265
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2009
-
负责人:Vipul C Chitalia
-
依托单位:
Role of Wnt signaling in uremia-induced entothelial dysfunction
-
批准号:7589925
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2009
-
负责人:Vipul C Chitalia
-
依托单位:
Role of Wnt signaling in uremia-induced entothelial dysfunction
-
批准号:8511611
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2009
-
负责人:Vipul C Chitalia
-
依托单位:
Role of Wnt signaling in uremia-induced entothelial dysfunction
-
批准号:7807040
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2009
-
负责人:Vipul C Chitalia
-
依托单位:
Role of Wnt signaling in uremia-induced entothelial dysfunction
-
批准号:8298601
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2009
-
负责人:Vipul C Chitalia
-
依托单位:
海外基金