Characterization of the Vitamin D System in Normal and Hypertrophied Heart

正常和肥厚心脏中维生素 D 系统的特征

• 批准号: 7156366
• 负责人: DENIS J GLENN
• 金额: $ 5.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156366
• 关键词: 1,25 dihydroxycholecalciferol; RNA interference; cardiac myocytes; cardiovascular pharmacology; cytochrome P450; enzyme activity; enzyme induction /repression; fibroblasts; gene deletion mutation; genetically modified animals; heart enlargement; laboratory mouse; polymerase chain reaction; postdoctoral investigator; receptor expression; tissue /cell culture; vitamin D receptors

DESCRIPTION (provided by applicant): Vitamin D directly inhibits key phenotypic features of cardiac hypertrophy raising the possibility that it may function in an autocrine or paracrine fashion to suppress hypertrophy. However, for this hypothesis to be valid requires that cardiac cells possess the ability to regulate and respond to the active form of vitamin D. The components of the vitamin D system, specifically the VDR, 1 alpha-hydroxylase and 24-hydroxylase, will be examined and the response to hypertrophic stimuli characterized. The importance of vitamin D in cardiovascular function is supported by studies of the vitamin D receptor (VDR) knockout mouse, which develops cardiac hypertrophy. However, the underlying mechanisms involved are difficult to interpret given the pleiotropic effect of vitamin D. To determine the direct effects of endogenous vitamin D on the myocyte will require a tissue specific model, and so a cardiac-selective deletion of the murine VDR gene will be created and the response to a hypertrophic stimulus will be assessed in vivo.

描述（由申请人提供）：维生素D直接抑制心脏肥厚的关键表型特征，提高了它可能以自分泌或旁分泌方式抑制肥厚的可能性。然而，为了使这一假设有效，需要心脏细胞具有调节和响应活性形式维生素D的能力。维生素D系统的组成部分，特别是VDR， 1 α -羟化酶和24-羟化酶，将被检查，并对增生性刺激的反应进行表征。维生素D在心血管功能中的重要性得到了维生素D受体（VDR）敲除小鼠的研究的支持，这些小鼠会发生心脏肥厚。然而，考虑到维生素D的多效性，所涉及的潜在机制很难解释。为了确定内源性维生素D对心肌细胞的直接影响，需要一个组织特异性模型，因此将创建小鼠VDR基因的心脏选择性缺失，并将在体内评估对肥厚刺激的反应。