PATHWAY PHARMACOGENETICS AND ANGIOTENSIN RECEPTOR BLOCKER RESPONSES

通路药物遗传学和血管紧张素受体阻滞剂反应

• 批准号: 7950752
• 负责人: AMBER L BEITELSHEES
• 金额: $ 0.34万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950752
• 关键词: Affect; Angiotensin II; Angiotensin Receptor; Atherosclerosis; Cardiac; Cardiovascular Diseases; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Dyslipidemias; Evaluation; Exhibits; Funding; Genes; Genetic; Genotype; Glucose; Grant; Hypertrophy; Inflammatory; Injury; Institution; Insulin Resistance; Mediating; Mediator of activation protein; Metabolic; Metabolic syndrome; Modality; Molecular; Myocardial; Myocardial Infarction; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacogenetics; Phase; Phenotype; Plasma; Property; Research; Research Personnel; Resources; Role; Running; Source; Structure; Subgroup; United States National Institutes of Health; adiponectin; cardiovascular risk factor; improved; lipid metabolism; patient population; response; telmisartan

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Through both angiotensin II-blocking and non-angiotensin II-mediated properties, angiotensin receptor blockers (ARBs) favorably affect glucose and lipid metabolism, adipocytokines and cardiac structure and function. to the extent that ARBs exhibit multiple beneficial effects that improve cardiovascular (CV) risk profiles, these agents represent a potentially important treatment modality for diverse patient populations. However, as with most drug classes, patients display tremendous variability in response to ARBs. Recent evidence suggests that ARBs increase plasma concentrations of the anti-atherosclerotic adipocytokines adiponectin. This effect is important given adiponectin's central role in protecting against insulin resistance, dyslipidemia, atherosclerosis, myocardial hypertrophy, and ischemic injury. In fact, adiponectin is an upstream effector of several molecular pathways that mediate myriad inflammatory and metabolic bioprocesses. As such, ADIPOQ, the gene that encodes adiponectin, is a strong candidate mediator of response to ARBs, and genetic variability in ADIPOQ could plausibly alter drug responses. Herein, we propose a fixed-sequence, run-in phase clinical study of the ARB telmisartan with in-depth metabolic phenotype and genotype characterization in post-myocardial infarction patients with features of the metabolic syndrome. We propose a comprehensive evaluation of ADIPOQ in order to determine which genetic subgroup(s) of patients might derive the greatest benefit from telmisartan with respect to molecular and myo-dimensional endpoints important in CV disease progression.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 通过血管紧张素II阻断和非血管紧张素II介导的特性，血管紧张素受体阻滞剂（ARB）有利地影响葡萄糖和脂质代谢，脂肪细胞因子以及心脏结构和功能。 在ARB表现出多种有益作用以改善心血管（CV）风险概况的范围内，这些药物代表了不同患者人群的潜在重要治疗方式。 但是，与大多数药物类别一样，患者对ARB的响应显示出巨大的可变性。 最近的证据表明，ARB会增加抗动脉粥样硬化脂肪细胞因子脂联素的血浆浓度。 鉴于脂联素在防止胰岛素抵抗，血脂异常，动脉粥样硬化，心肌肥大和缺血性损伤方面的核心作用，这种作用很重要。 实际上，脂联素是几种介导无数炎症和代谢生物过程的几种分子途径的上游效应子。 因此，编码脂联素的基因Adipoq是对ARB的反应的强大候选介质，而adipoq的遗传变异性可以显着改变药物反应。 本文中，我们提出了对ARB telmisartan的固定序列临床研究，具有深入的代谢表型和具有代谢综合征特征的腰椎后梗死患者的深入代谢表型和基因型表征。 我们提出对ADIPOQ的全面评估，以确定哪些遗传亚组的患者可能会从Telmisartan中获得最大的收益，从而在分子和Myo二维终点中对CV疾病进展很重要。