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的主要死亡原因，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，许多人需要持续的药物治疗。密西西比州的心血管疾病的年年龄调整死亡率是美国所有州中最高的。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，但其他因素也可能起作用。环境毒物在心血管疾病中的作用越来越受到重视。密西西比的经济以农业为主，大部分人口居住在靠近农作物种植地的农村地区。这种接近导致人们接触目前使用的农药以及遗留农药，这些农药在过去使用，但在今天的环境中持久存在。最近的研究表明，暴露于毒死蜱，一种有机磷杀虫剂，在子宫内可以影响腺苷酸环化酶信号通路的心肌细胞。然而，很少有人知道农药对心血管疾病的发展，进展和药物治疗的影响。这项资助计划用于研究狄氏剂和毒死蜱这两种与环境相关的杀虫剂对大鼠心脏蛋白质组的影响。狄氏剂是一种在20世纪50年代和60年代广泛使用的传统杀虫剂（尽管目前在美国被禁止）。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杀虫剂。这项资助的目的是鉴定那些通过暴露于这两种杀虫剂而改变转录和/或翻译后修饰水平的蛋白质。因此，确定的蛋白质将用于指导进一步的研究，旨在确定这些农药的毒性机制。我们的长期目标是更好地了解常用农药和其他环境化学品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.