Early Life Stress Induced Mechanisms of Cardiovascular Disease Risk and Resilience

生命早期压力诱发心血管疾病风险和恢复力的机制

• 批准号: 10555121
• 负责人: Jennifer S Pollock
• 金额: $ 224.27万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10555121
• 关键词: Address; Adolescence; Adolescent; Adult; Animal Model; Basic Science; Bioinformatics; Biometry; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Central Nervous System; Child; Child Rearing; Clinic; Clinical; Collaborations; Data; Data Analytics; Diastolic blood pressure; Diet; Economics; Elderly; Endothelium; Ensure; Europe; Exposure to; Functional disorder; Future; Goals; Grant; Health; Healthcare; Heart Rate; Household; Human; Hypertension; Individual; Inflammation; Inflammation Mediators; Inflammatory; Intervention; Life; Life Stress; Macrophage; Manuscripts; Measurement; Mediating; Mentors; Mission; Molecular; National Heart, Lung, and Blood Institute; North America; Peripheral; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Physical activity; Physiologic pulse; Prevention; Prevention strategy; Program Research Project Grants; Psychological Stress; Publications; Recording of previous events; Reproducibility; Risk; Risk Factors; Rodent; Rodent Model; Sampling; Sexual abuse; Specimen; Stressful Event; Structure; System; Techniques; Technology; Telemetry; Temperature; Translating; Translations; Vascular Diseases; Vascular Endothelium; Vascular resistance; Work; abuse neglect; blood pressure control; cardiovascular disorder risk; care burden; circadian; clinically relevant; cost; data management; disorder risk; early life stress; effective therapy; emerging adult; epigenome; experience; gut microbiome; immune activation; insight; lifestyle factors; metabolome; monocyte; multiple omics; neural network; novel; physical abuse; programs; prospective; protective factors; resilience; stressor; synergism; transcriptome; translational potential; translational study; traumatic event; violence exposure

OVERALL SUMMARY Early life stress (ELS) is defined as stressful and traumatic events, such as household dysfunction, neglect, sexual or physical abuse, economic hardship, and exposure to violence, experienced up to 18 years. ELS was identified as a cardiovascular disease (CVD) risk factor over 20 years ago, but mechanistic insights into its effects remain very limited. Exposure to ELS is pervasive in the US with ~50% of children and adolescents having one or more major ELS experiences. ELS exposure increases the risk traditional CVD risk factors - by the 3rd-4th decade of life. A recent analysis of healthcare burden in Europe and North America attributed $748 billion in annual costs to the effects of ELS, with 75% of those costs in people with multiple ELS exposures. The significance of our work aligns with the NHLBI mission to promote the prevention and treatment of cardiovascular diseases enhancing the health of all individuals to live longer and fulfilling lives. Among individuals with a history of ELS exposure, vascular dysfunction (elevated peripheral vascular resistance, increased vascular stiffness) and elevated diastolic blood pressure are already evident in early adulthood. The overall goal of our program project grant (PPG) is to define mechanisms by which ELS leads to CVD risk and inform strategies for prevention and effective treatment of CVD consequences in individuals exposed to ELS. This PPG will address two critical barriers to fulfill our goal: 1) Need for ELS-specific in-depth mechanistic and translational studies; and, 2) Identify modifiable protective factors that can reduce ELS-induced CVD risk. The overarching hypothesis of our PPG is that ELS induces immune cell activation leading to vascular dysfunction with increased hypertension risk and CVD risk that are exacerbated by later life stressors or moderated by resilience/protective factors. This PPG with both basic science and clinical projects utilizes a synergistic and integrative approach translating concepts from clinically relevant rodent models to humans. Our group is extremely synergistic, with each leader bringing unique expertise from different scientific backgrounds focused on our overall goal to understand mechanisms of ELS induced indicators of CVD risk and resilience. Over the past several years, our team built strong collaborations translating discoveries between basic and clinical labs with several pilot grants, co-mentoring trainees, and multiple jointly authored abstracts, manuscripts, and publications. The four projects and three cores are integrated in their goals and impact such that much more will be achieved together than separately. This PPG utilizes a range of approaches to investigate in-depth molecular mechanisms of ELS-induced hypertension and vascular disease risk as well as to delineate protective factors mediating resiliency to this risk. The results will have important translational potential pointing to new intervention or prevention strategies for the health consequences of CVD and reducing the healthcare burden of CVD.

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