Vitamin D and Cardiovascular Disease

描述(由申请人提供)： 维生素D缺乏和心血管疾病(CVD)都是非常普遍的疾病。虽然人们对心血管疾病的病因和治疗有很多了解，但关于维生素D对心血管的影响的数据很少。几十年来，人们已经知道维生素D(25(OH)D3)是由肾脏转化为活性激素1，25(OH)2D3的。一旦转化，1，25(OH)2D3能够与多种细胞类型的核维生素D受体(VDR)结合，包括肠上皮细胞、甲状旁腺细胞和肾小管细胞，随后是特异的基因转录。然而，最近，VDR明显存在于其他关键细胞类型中，包括巨噬细胞、血管内皮细胞和心肌细胞。这些数据支持维生素D在心血管健康中的作用。虽然这一主题尚未成为心血管疾病研究的主流，但新出现的生物学和临床联系表明，维生素D和心血管疾病专家之间的更强有力的合作可能会产生治疗心血管疾病的新研究和潜在疗法。我们的目标是制定一份共识文件，强调将维生素D和心血管疾病联系起来的生物学和临床证据，以及将维生素D疗法带给各种形式心血管疾病患者的潜在研究战略。为了实现这一目标，来自美国各地的著名维生素D和心血管疾病专家和有前途的年轻研究人员将于2008年10月齐聚波士顿，参加为期1.5天的名为维生素D与心血管疾病的全国研讨会。我们的目标是：1.严格检查现有的将维生素D缺乏和心血管疾病联系起来的基础科学和临床证据；2.检查导致心血管疾病的新途径，并确定这些过程如何与VDR激活的不断增长的生物学联系在一起；3.确定如何将维生素D生物学转化为临床研究和心血管疾病患者的潜在治疗选择。据我们所知，这次拟议的研讨会将是第一次将维生素D和心血管疾病联系起来的研讨会。本次研讨会将主要由NHLBI提供支持，所有剩余的支持都将得到强有力的机构承诺。重要的是，我们将邀请(并支付费用)来自美国各地的20名年轻科学家在这次研讨会上展示他们的工作(口头和海报)。研讨会将在马萨诸塞州综合医院的校园内举行，我们预计来自全美的75名与会者，以及那些有特殊需求的人将得到适当的安排。这项建议的PI和共同调查者指导医院的D受体激活研究中心(CEDAR)，并在这一领域发表了大量的论文。此外，他们过去有高质量有效规划和实施类似研讨会的经验，并成功地制定了共识文件供发表。在这项提案的所有阶段(规划、发言者、工作组)，妇女和代表性不足的少数群体都有很好的代表性，协商一致的文件将在一份著名的心脏病学杂志上发表。最后，这次研讨会将为计划和提议在波士顿会议后18-24个月内的全国心脏病学会议上举行一次更大的会议提供基础；该活动将得到Cedar的支持。

DESCRIPTION (provided by applicant): Both vitamin D deficiency and cardiovascular disease (CVD) are highly prevalent disorders. Although much is known about the etiology and treatment of CVD, there are sparse data on the cardiovascular effects of vitamin D. For decades, it has been known that Vitamin D (25(OH)D3) is converted to the active hormone 1,25(OH)2D3 by the kidney. Once converted, 1,25(OH)2D3 is capable of binding to the nuclear vitamin D receptor (VDR) in a variety of cell types including the gut epithelia, parathyroid cells, and kidney tubular cells, and specific gene transcription follows. More recently, however, it has become apparent that the VDR exists in other critical cell types including macrophages, smooth muscle and endothelial cells, and cardiac myocytes. These data support the involvement of vitamin D in cardiovascular health. Although the topic is not yet in the mainstream of CVD research, the emerging biological and clinical links suggest novel research and potential therapies for CVD that may emerge from stronger collaborations between Vitamin D and CVD experts. Our goal is to develop a consensus document highlighting the biological and clinical evidence linking vitamin D and CVD, and potential research strategies for bringing vitamin D therapies to patients with various forms of CVD. To accomplish this goal, renowned Vitamin D and CVD experts and promising young investigators from throughout the US will converge in Boston for a 1.5-day national symposium entitled Vitamin D and Cardiovascular Disease in October, 2008. Our objectives will be to: 1. To critically examine the existing basic science and clinical evidence linking vitamin D deficiency and CVD; 2. To examine novel pathways leading to CVD, and to determine how these processes may be linked with the growing biology of VDR activation; 3. To define how vitamin D biology can be translated to clinical studies and potential therapeutic options for patients with CVD. To our knowledge, this proposed symposium will be the first of its kind to link Vitamin D and CVD. This symposium will be primarily supported by NHLBI, and there is strong institutional commitment for all the remaining support. Importantly, we will invite (and pay expenses for) 20 young scientists from throughout the US to present their work (orally and by posters) at this symposium. The symposium will take place on the campus of the Massachusetts General Hospital, we expect 75 attendees from throughout the US, and those with special needs will be appropriately accommodated. The PI and Co-Investigator of this proposal direct the hospital's Center for D-receptor Activation Research (CeDAR), and have published extensively in this area. Moreover, they have past experience in efficiently planning and implementing similar symposia of high quality, and they have successfully developed consensus documents for publication. There is excellent representation of women and under-represented minorities in all phases of this proposal (Planning, Speakers, Working Group), and the consensus document will be published in a prominent cardiology journal. Finally, this symposium will provide the foundation for planning and proposing a larger meeting at a national cardiology meeting within 18-24 months of the Boston event; this event will be supported by CeDAR.