ION CHANNEL DETERMINANTS OF MAST CELL ACTION IN THE HEART

心脏肥大细胞作用的离子通道决定因素

• 批准号: 8360591
• 负责人: Alexander James Stokes
• 金额: $ 27.51万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360591
• 关键词: Affect; American; Calcium; Calcium Channel; Cannabinoids; Cardiac; Cardiomyopathies; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Cells; Centers of Research Excellence; Cessation of life; Chemicals; Funding; Grant; Heart; Heart Hypertrophy; Heart failure; Hypertrophy; Ion Channel; Knock-out; Knockout Mice; Medical; Medical Economics; Modeling; National Center for Research Resources; Pathology; Pharmaceutical Preparations; Principal Investigator; Reagent; Research; Research Infrastructure; Resources; Signal Transduction; Source; TRPV1 gene; United States National Institutes of Health; cannabinoid receptor; cost; economic impact; mast cell; new therapeutic target; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Eighty-one million Americans are affected by at least one type of cardiovascular disease. In 2010 heart failure will contribute to 1 in 8 deaths and cost $40 billion in medical expenses. The staggering medical and economic impact of cardiac pathologies creates a compelling justification to find and study new therapeutic targets. Here we will study two calcium channels in the context of cardiac hypertrophy and toxic cardiomyopathy. The first is the ionotropic cannabinoid receptor, TRPV1, which is a critical determinant of calcium entry in response to both cannabinoids and physico-chemical signals. The second is CRACM1, a calcium release-activated calcium channel, which allows calcium entry into cells following depletion of the intracellular stores. Our central hypothesis is that knockout and inhibition of TRPV1 and CRACM1 can protect the heart from hypertrophy and alleviate drug induced toxic cardiopathies. The overall objective of the proposed research is to identify reagents that could potentially protect the heart from i) hypertrophy and ii) cardiotoxicity. The proposed experiments utilize Trpv1 and Cracm1 knockout mice, and existing TRPV1 antagonists, in a model of cardiac hypertrophy, and toxic cardiopathy, to identify the contribution of TRPV1 and CRACM1 activation in these pathologies.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 八十百万美国人受到至少一种心血管疾病的影响。 在2010年，心力衰竭将造成8人中的1人，造成400亿美元的医疗费用。心脏病理的惊人医疗和经济影响为寻找和研究新的治疗靶标提供了令人信服的理由。 在这里，我们将在心脏肥大和有毒心肌病的背景下研究两个钙通道。第一个是离子型大麻素受体TRPV1，这是响应大麻素和物理化学信号的钙进入的关键决定因素。第二个是CRACM1，这是一种钙释放激活的钙通道，它允许钙进入细胞内存储后钙进入细胞。 我们的中心假设是，TRPV1和CRACM1的敲除和抑制可以保护心脏免受肥大的影响，并减轻药物诱导的有毒心脏病。拟议的研究的总体目标是确定可能保护心脏免受I）肥大和II）心脏毒性的试剂。提出的实验利用TRPV1和CRACM1基因敲除小鼠，以及现有的TRPV1拮抗剂，在心脏肥大的模型和有毒的心脏病模型中，以确定这些病理学中TRPV1和CRACM1激活的贡献。