COVID-19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19
COVID-19:HDL 在 COVID-19 的先天免疫和心血管保护中的作用
基本信息
- 批准号:10153344
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAcute-Phase ReactionAdult Respiratory Distress SyndromeAgeAnti-Bacterial AgentsAnti-Inflammatory AgentsAntiviral AgentsApolipoprotein A-IApolipoprotein EAtherosclerosisBacterial InfectionsBasic ScienceBiological AssayBiologyCOVID-19COVID-19 assayCOVID-19 mortalityCOVID-19 patientCardiovascular DiseasesCardiovascular systemCause of DeathCessation of lifeCholesterolClinicalClinical TrialsCollaborationsCoronavirusDangerousnessDataDevelopmentDiabetes MellitusDiseaseEpithelial CellsFunctional disorderGoalsHIVHIV InfectionsHeart DiseasesHepaticHigh Density Lipoprotein CholesterolHigh Density LipoproteinsHypertriglyceridemiaImmunologyImpairmentInfectionInflammationInflammatoryInflammatory ResponseInfluenzaInnate Immune SystemInterferon-betaIntrinsic factorKnowledgeLeadLipidsLipoproteinsLungMediatingMembrane FusionMetabolicMorbidity - disease rateNatural ImmunityNon-Insulin-Dependent Diabetes MellitusObesityOutcomePathway interactionsPatientsPeptidesPlayProductionPropertyProteinsProteomicsRecombinantsRiskRoleRunningSARS-CoV-2 infectionSamplingScaffolding ProteinSepsisSymptomsTestingTherapeuticTroponinUnited StatesVeteransViralVirus DiseasesVirus Replicationcoronavirus diseasecytokinehigh riskimprovedinnovationlipidomicsmacrophagemortalitynovel coronavirusparticlepeptidomimeticsprotein expressionproteomic signatureresponsesevere COVID-19symptomatic COVID-19systemic inflammatory responsetargeted treatment
项目摘要
COVID19: HDL’s Role in Innate Immunity and Cardiovascular Protection with COVID-19
The novel coronavirus (SARS-CoV-2) causes a disease called COVID-19. For many people, COVID-19 has
almost no symptoms, yet for others, COVID-19 is particularly dangerous and has high morbidity and mortality
rates. People with pre-existing type-2 diabetes and atherosclerotic cardiovascular disease (ASCVD) have twice
the risk of SARS-CoV-2 infection and are more likely to have poor outcomes. 70% of patients with ASCVD and
elevated troponin die of COVID. We don’t know what intrinsic factors contribute to these disparate outcomes.
High Density Lipoprotein (HDL) particles play a critical role in the innate immune system and are protective
against viral and bacterial infections. HDL particles best are known for their roles protecting from atherosclerotic
cardiovascular disease (ASCVD). The cardiovascular protection conferred by HDL is largely mediated by HDL’s
associated proteins, which comprise about half of HDL’s mass. Mechanisms for HDL’s protection from ASCVD
are shared with mechanisms for HDL’s protection from viral infections. These protective properties center around
the HDL-associated proteins that mediate its anti-inflammatory and antioxidative functions. The goal of this
project is to define how HDL may protect from Sars-CoV-2 infection and limit the inflammatory response to
COVID-19 illness. Obesity and type-2 diabetes (DM2) lead to hypertriglyceridemia and metabolic changes that
impair HDL’s anti-inflammatory and antioxidative functions. We will define if DM2 leads to HDL dysfunction and
contributes to severe COVID-19 outcomes.
Our overarching hypothesis is that HDL’s antiviral properties can limit SARS-CoV-2 infection and that HDL’s
anti-inflammatory and antioxidative capacity limit the systemic inflammatory response to COVID-19. We have
initiated a collaboration with Dr. Malall, an immunology expert running a large trial with COVID-19 patients whose
de-identified samples are paired with de-identified EMR outcomes data. In AIM1 we will test the hypothesis that
SARS-CoV-2 infection impairs HDL’s antioxidative and anti-inflammatory capacities, and that these changes can
be predicted by proteomic signatures of HDL. We also have collaboration with Dr. Denison, an expert in
coronavirus biology. In AIM2 we will test the hypothesis that HDL can reduce SARS-CoV-2 infectivity of lung
epithelial cells, but that COVID-19 impairs HDL’s antiviral capacity, which can be improved with Remdesavir
treatment. In AIM3 we will test the hypothesis that type-2 diabetes alters the HDL-associated protein networks
that limit systemic inflammation with COVID-19 and protect against SARS-CoV-2 infection.
Diabetes and cardiovascular disease are among the most prevalent problems among United States
Veterans, making Veterans more likely to have poor COVID-19 outcomes. An asset to this project is that we can
relate our HDL function and antiviral assays with clinical outcomes. Our studies will define proteomic signatures
from HDL that are important for its antiviral effects. We ultimately aim to use HDL-directed therapies like
recombinant Apo-A1 peptides to improve COVID outcomes.
COVID-19: HDL在COVID-19先天性免疫和心血管保护中的作用
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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John Michael Stafford其他文献
John Michael Stafford的其他文献
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{{ truncateString('John Michael Stafford', 18)}}的其他基金
COVID-19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19
COVID-19:HDL 在 COVID-19 的先天免疫和心血管保护中的作用
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10404924 - 财政年份:2021
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CETP 与代谢和心血管疾病的性别差异
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10407032 - 财政年份:2019
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Therapeutic Potential of Estrogen-Regulated Metabolism and Cardiovascular Risk
雌激素调节代谢和心血管风险的治疗潜力
- 批准号:
10184832 - 财政年份:2016
- 资助金额:
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Estrogen and coordinated carbohydrate and lipid metabolism in obesity
肥胖中的雌激素与碳水化合物和脂质代谢的协调
- 批准号:
9222748 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Therapeutic Potential of Estrogen-Regulated Metabolism and Cardiovascular Risk
雌激素调节代谢和心血管风险的治疗潜力
- 批准号:
10899800 - 财政年份:2016
- 资助金额:
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Therapeutic Potential of Estrogen-Regulated Metabolism and Cardiovascular Risk
雌激素调节代谢和心血管风险的治疗潜力
- 批准号:
10392424 - 财政年份:2016
- 资助金额:
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Therapeutic Potential of Estrogen-Regulated Metabolism and Cardiovascular Risk
雌激素调节代谢和心血管风险的治疗潜力
- 批准号:
10618133 - 财政年份:2016
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Cholesteryl ester transfer protein, a novel mediator of insulin sensitivity
胆固醇酯转移蛋白,一种新型胰岛素敏感性介质
- 批准号:
8966663 - 财政年份:2013
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Cholesteryl ester transfer protein, a novel mediator of insulin sensitivity
胆固醇酯转移蛋白,一种新型胰岛素敏感性介质
- 批准号:
8633281 - 财政年份:2013
- 资助金额:
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