The Effect of a Mixture of Pesticides on the Rat Cardiac Proteome

描述（由申请人提供）：心血管疾病是当今美国死亡的主要原因，并且在上个世纪一直如此。大约有7000万美国人患有某种形式的心血管疾病，其中许多人需要持续的药物治疗。在美国各州中，密西西比州每年因心血管疾病导致的年龄调整死亡率最高，已知的心血管疾病风险因素可能是造成这种差异的主要原因，但其他因素可能也起了作用。环境毒物在心血管疾病中的作用越来越被认识到。密西西比州的经济以农业为基础，大部分人口居住在靠近农作物种植地的农村地区。这种接近导致人口接触到当前使用的农药以及遗留农药，这些农药过去使用过，但在今天的环境中持续存在。最近的研究表明，在子宫内暴露于毒死蜱（一种有机磷杀虫剂）可以影响心肌细胞中的腺苷酸环化酶信号通路。然而，农药对心血管疾病的发生、进展和药物治疗的影响知之甚少。这项拨款旨在研究两种与环境有关的杀虫剂，狄氏剂和毒死蜱对大鼠心脏蛋白质组的影响。狄氏剂是上世纪五六十年代广泛使用的一种遗留农药（尽管目前在美国被禁止使用），它仍然存在于密西西比三角洲地区的土壤样本中。毒死蜱是目前使用的一种农药。这项资助的目的是鉴定暴露于这两种农药后转录和/或翻译后修饰水平发生改变的蛋白质。由此确定的蛋白质将用于指导旨在确定这些农药毒性机制的进一步研究。我们的长期目标是更好地了解常用杀虫剂和其他环境化学物质对心脏病及其治疗的影响程度。

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the U.S. today and has been so for the last century. Approximately 70 million Americans suffer from some form of cardiovascular disease and many require ongoing pharmacological therapy. Mississippi has the highest annual age-adjusted death rate from cardiovascular disease of any state in the U.S. Known risk factors for cardiovascular disease probably account for much of this disparity but other factors may be playing a role. Increasingly, the role of environmental toxicants in cardiovascular disease is being recognized. Mississippi has an agricultural based economy and much of the population resides in rural settings close to where crops are grown. This proximity results in the contact of the population with current use pesticides as well as legacy pesticides, those pesticides used in the past but persistent in the environment today. Recent studies have shown exposure to chlorpyrifos, an organophosphate insecticide, in utero can affect the adenylyl cyclase signaling pathway in cardiac myocytes. However, little is known about the effect of pesticides on the development, progression, and pharmacological treatment of cardiovascular disease. This grant proposes to examine the effects of two environmentally relevant pesticides, dieldrin and chlorpyrifos, on the rat cardiac proteome. Dieldrin is a legacy pesticide used extensively in the 1950's and 1960's (though currently banned in the U.S.) which is still present in soil samples from the Mississippi Delta region. Chlorpyrifos is a pesticide in current use. The goal of this grant is to identify proteins whose levels of transcription and/or post-translational modifications are altered by exposure to these two pesticides. The proteins thus identified will serve to direct further studies aimed at identifying the mechanism of toxicity of these pesticides. Our long-term objective is to better understand the extent to which commonly used pesticides and other environmental chemicals influence heart disease and its treatment.