Endocrine Disruptors and Heart Health

内分泌干​​扰物与心脏健康

• 批准号: 10251514
• 负责人: Jack Rubinstein
• 金额: $ 5.17万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251514
• 关键词: Administrative Supplement; African-American Graduate Student; Animals; Area; Attention; Blood coagulation; Cardiac; Cardiac health; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Categories; Chemicals; Coagulation Process; Electrophysiology (science); Endocrine Disruptors; Environmental Health; Environmental Impact; Estrogens; Exposure to; Fostering; Future; Goals; Gonadal Hormones; Health; Heart; Hemostatic function; Human; Ischemic Stroke; Laboratories; Life; Link; Minority Graduate Student; Myocardial Infarction; Physiology; Process; Pulmonary Embolism; Regulation; Reporting; Research; Research Project Grants; Research Technics; Risk; Rodent; Thrombosis; Toxic effect; Toxicology; Training; Underrepresented Minority; analog; bisphenol A; career; design; electrical property; environmental chemical; environmental toxicology; epidemiology study; experimental study; innovation; thrombotic

SUMMARY/ABSTRACT This application seeks administrative supplement, under the Research Supplements to Promote Diversity in Health-Related Research category (PA 20-222), to provide support for Latia Tucker, an African American graduate student in my laboratory. Her graduate research project focuses on the impact of environmental disrupting chemicals (EDCs) on the cardiovascular-circulatory system, including the heart and blood coagulation. Bisphenol A (BPA) and its related analogues are common EDCs with a range of potential adverse health effects. Growing epidemiologic and experimental studies have demonstrated a potential link between higher BPA exposure and cardiovascular diseases. In previous studies, my laboratory reported some of the first evidence on the arrhythmogenic actions of BPA in rodent hearts. We further showed that the pro-arrhythmic effects of BPA was shared by its analogue chemical bisphenol S (BPS). Our findings demonstrate the potential cardiovascular toxicity of BPA, and highlight the need to further define the impact of BPA and related EDCs on human heart health. While the cardiac toxicities of bisphenol chemicals have received increasing attention, an area that is currently completely unknown is the potential impact of these chemicals on hemostasis. Increased blood coagulation leads to thrombosis, which can result in life threatening conditions including myocardial infarction (heart attack), ischemic stroke, and pulmonary embolism. Importantly, it has been well established that gonadal hormones impact blood coagulation; in particular, estrogen has been shown to increase coagulation. However, the potential influence of environmental chemicals, including EDCs, on these processes is entirely unknown. The overall goal of Latia's thesis research is to determine the impact of both BPA and a mixture of BPA analogue chemicals on the circulatory system. Her study will focus on 1) the impact of these chemicals on cardiac electrical properties and markers of electrical abnormality in the hearts of larger animals; and 2) the effects of exposure to BPA and a mixture of BPA-related bisphenols on blood coagulation and thrombotic risks. These studies are innovative and has high significance, and will provide important understanding of the potential cardiovascular-circulatory toxicity of bisphenol type EDCs. They will also provide comprehensive training for Latia on environmental health and toxicology, cardiac physiology and electrophysiology, and hemostasis regulation, thus equipping her well for pursuing future independent research career.

摘要/摘要 本申请寻求行政补充，根据《促进研究补充》 健康相关研究类别的多样性 (PA 20-222)，为 Latia Tucker 提供支持， 我实验室的一名非裔美国研究生。她的研究生研究项目重点 环境破坏化学物质 (EDC) 对心血管循环的影响 系统，包括心脏和血液凝固系统。双酚 A (BPA) 及其相关类似物 是常见的 EDC，具有一系列潜在的不良健康影响。日益增长的流行病学和 实验研究表明，较高的 BPA 暴露与 心血管疾病。在之前的研究中，我的实验室报告了一些最初的证据 BPA 对啮齿动物心脏的致心律失常作用。我们进一步表明，促心律失常 BPA 的作用与其类似化学物质双酚 S (BPS) 具有相同的作用。我们的研究结果表明 BPA 的潜在心血管毒性，并强调需要进一步确定其影响 BPA 和相关 EDC 对人类心脏健康的影响。而双酚化学物质的心脏毒性 受到越来越多的关注，目前完全未知的领域是潜力 这些化学物质对止血的影响。血液凝固增加会导致血栓形成， 可能导致危及生命的疾病，包括心肌梗塞（心脏病发作）、缺血性心脏病 中风和肺栓塞。重要的是，性腺激素已被证实 影响血液凝固；特别是，雌激素已被证明可以促进凝血。 然而，环境化学品（包括 EDC）对这些过程的潜在影响 完全未知。 Latia 论文研究的总体目标是确定 BPA 和混合物的影响 BPA 类似化学品对循环系统的影响。她的研究重点是 1） 这些化学物质对心脏电特性和心脏电异常标志物有影响 较大的动物； 2) 接触 BPA 和 BPA 相关双酚混合物的影响 凝血和血栓风险。这些研究具有创新性和重要意义， 并将提供对潜在心血管循环毒性的重要了解 双酚型EDC。他们还将为拉蒂亚提供全面的环境培训 健康和毒理学、心脏生理学和电生理学以及止血调节，因此 为她未来的独立研究生涯做好准备。