Prospective Effects of Early Life Stress and Protective Factors on Vascular Function and Inflammation in Young Adulthood
早期生活压力和保护因素对青年期血管功能和炎症的前瞻性影响
基本信息
- 批准号:10555128
- 负责人:
- 金额:$ 36.51万
- 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
- 起止时间:2023-02-15 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:AdolescenceAdolescentAdultAdverse eventAgeAlabamaAmericanAnimal ModelAnimalsAortaBiologicalBlood PressureBlood VesselsC-reactive proteinCardiovascular DiseasesCardiovascular systemChild RearingColony-Stimulating FactorsDataDevelopmentDietEvaluationEvidence based interventionExposure toFutureGene ExpressionGenetic TranscriptionHDAC9 geneHeart RateHistone DeacetylaseHumanHypertensionImmuneImmune System DiseasesImmune systemIndividualInflammationInflammatoryInterleukinsInterventionKnowledgeLeadLife StyleLinkMacrophage Colony-Stimulating FactorMeasuresMediatingMediationMethylationModelingMolecularNADPH OxidaseOutcomePathway interactionsPeripheral Blood Mononuclear CellPersonsPhysical activityPhysiologicalPsychosocial FactorRisk FactorsRodentRodent ModelRoleStressTNF geneTestingTimeTissue-Specific Gene ExpressionUp-RegulationVascular DiseasesVascular SystemVolatile Fatty Acidsblood pressure variabilitycardiovascular disorder preventioncardiovascular disorder riskcardiovascular risk factorcohortcritical developmental periodcytokineearly experienceearly life stressethnic diversityexperiencegut microbiomeindexinginflammatory markerinnovationlifestyle factorsmetabolomemetabolomicsmethylomemicrobiomemicrobiome compositionmultiple omicsnovelpreventprospectiveprotective factorsresiliencesynergismtranscriptomeyoung adult
项目摘要
PROJECT 4 SUMMARY
Early life stress (ELS), defined as adverse experiences occurring before age 18, is a highly prevalent risk
factor for cardiovascular disease (CVD). However, the development of effective strategies to prevent
CVD in individuals exposed to ELS is hindered by lack of knowledge about physiological pathways
underlying ELS effects on CVD, as well as malleable lifestyle factors that may mitigate these effects.
Cross-species animal studies guiding Project 1 and Project 2 implicate specific mechanistic pathways
that link ELS with CVD, including upregulation of histone deacetylase 9 (HDAC9), NADPH oxidase 2
(NOX2), and cytokines; reduced diversity in the gut microbiome; and reduction of short-chain fatty acids
(SCFA). Together, these pathways induce CVD through reprogramming of the immune and vascular
system in rodent models of ELS. However, we do not know whether these pathways lead to CVD in
people who experienced ELS and whether they can be modified by lifestyle factors, such as diet,
physical activity, and supportive parenting, during development. Project 4 will leverage an existing,
ethnically diverse cohort of 1,000 adults (age 29) from Birmingham, Alabama, who have been
characterized for ELS and lifestyle factors at ages 11, 13, 16, and 19, to test the hypotheses that 1) ELS
induces vascular dysfunction and hypertension through sustained pro-inflammatory reprogramming of
the gut microbiome and peripheral blood mononuclear cell transcriptome, and that 2) these effects may
be modified by protective lifestyle factors during development. The proposed assessment at age 29 will
include a comprehensive evaluation of stress and lifestyle factors in adulthood; vascular function; gut
microbiome; SCFAs; and peripheral blood mononuclear cell (PBMC) transcriptome. Data from all five
time points spanning ages 11 to 29 will be integrated to test 1) the relationship between prospectively
measured ELS and immune and vascular function in adulthood; 2) whether these relationships are
mediated by pro-inflammatory profiles of the gut microbiome and PBMC transcriptome in adulthood; and
3) whether diet quality, physical activity, and supportive parenting during development modify the
relationships between ELS and adult gut microbiome, PBMC transcriptome, and immune and vascular
function. Project 4 is conceptually and translationally innovative by testing specific gut microbiome and
transcriptome pathways discovered in rodents in humans. Together with Project 3 which tests
complementary metabolome and methylome pathways in adolescence, the two human projects will guide
future mechanistic studies by identifying new multi-omic pathways that link ELS with vascular dysfunction
during critical developmental periods spanning adolescence to young adulthood. The integrated findings
from this PPG will elucidate causal pathways and protective factors related to ELS-induced CVD risk,
directly informing the development of novel evidence-based interventions.
项目四总结
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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Sylvie Mrug其他文献
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{{ truncateString('Sylvie Mrug', 18)}}的其他基金
Early Life Stress, DNA Methylation, and Health Disparities across Ages
早期生活压力、DNA 甲基化和各年龄段的健康差异
- 批准号:
10597116 - 财政年份:2021
- 资助金额:
$ 36.51万 - 项目类别:
Early Life Stress, DNA Methylation, and Health Disparities across Ages
早期生活压力、DNA 甲基化和各年龄段的健康差异
- 批准号:
10454426 - 财政年份:2021
- 资助金额:
$ 36.51万 - 项目类别:
Early Life Stress, DNA Methylation, and Health Disparities across Ages
早期生活压力、DNA 甲基化和各年龄段的健康差异
- 批准号:
10176902 - 财政年份:2021
- 资助金额:
$ 36.51万 - 项目类别:
Gender and Ethnicity in Early Substance Use Initiation
早期药物使用起始中的性别和种族
- 批准号:
7680176 - 财政年份:2008
- 资助金额:
$ 36.51万 - 项目类别:
Gender and Ethnicity in Early Substance Use Initiation
早期药物使用起始中的性别和种族
- 批准号:
8082133 - 财政年份:2008
- 资助金额:
$ 36.51万 - 项目类别:
Gender and Ethnicity in Early Substance Use Initiation
早期药物使用起始中的性别和种族
- 批准号:
8117737 - 财政年份:2008
- 资助金额:
$ 36.51万 - 项目类别:
Gender and Ethnicity in Early Substance Use Initiation
早期药物使用起始中的性别和种族
- 批准号:
7447148 - 财政年份:2008
- 资助金额:
$ 36.51万 - 项目类别:
Gender and Ethnicity in Early Substance Use Initiation
早期药物使用起始中的性别和种族
- 批准号:
7903987 - 财政年份:2008
- 资助金额:
$ 36.51万 - 项目类别:
Project 1: Early Life Stress, DNA Methylation, and Disparities in Obesity across Generations
项目 1:早期生活压力、DNA 甲基化和代际肥胖差异
- 批准号:
10648149 - 财政年份:2003
- 资助金额:
$ 36.51万 - 项目类别:
Project 1: Early Life Stress, DNA Methylation, and Disparities in Obesity across Generations
项目 1:早期生活压力、DNA 甲基化和代际肥胖差异
- 批准号:
10161623 - 财政年份:2003
- 资助金额:
$ 36.51万 - 项目类别:
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