NEUROPEPTIDE Y RECEPTORS AND VASCULAR REMODELING

描述：增殖和凋亡都伴随着血管 在高血压和动脉粥样硬化中发生的重塑。 而 已知交感神经是营养性的， 儿茶酚胺很弱。 目前的假设是神经肽Y (NPY)这些神经中的共递质是参与 血管平滑肌生长。 初步数据显示， NPY刺激生长和凋亡。 受体亚型及其作用机制 行动尚不清楚。 目标是：（1）进一步定义增长 NPY的作用，并了解促有丝分裂和凋亡之间的平衡 2）研究NPY代谢酶的调节， 与增长效应的联系，作为理解是否 这些酶可能参与调节生长与抗生长 影响; 3）确定受体的亚型和4）它们的信号传导 途径。 反义寡核苷酸将用于细胞培养，以阐明 与每个受体亚型相关的通路。 新受体的证据 将导致克隆新受体的努力。 （5）研究 NPY对大鼠颈动脉内膜增生的影响 用于检验损伤与以下因素的上调相关的假设： 血管中的NPY系统以及用拮抗剂治疗将 扭转这些影响。 这些研究将提供有用的信息， 开发新的抗有丝分裂疗法

DESCRIPTION: Both proliferation and apoptosis accompany the vascular remodeling that occurs in hypertension and atherosclerosis. While the sympathetic nerves are known to be trophic, the mitogenic effects of catecholamines are weak. The current hypothesis is that the neuropeptide Y (NPY) co-transmitter in these nerves is the major factor involved in vascular smooth muscle growth. Preliminary data are provided to show that NPY stimulates growth and apoptosis. The receptor subtype and mechanism of action are not yet known. The aims are to 1) further define the growth effects of NPY and to understand the balance between mitogenic and apoptotic effects; 2) study the regulation of the NPY metabolizing enzymes in association with the growth effects, as a means of understanding whether these enzymes might be involved in regulating the growth versus antigrowth effects; 3) determine the subtypes of receptors and 4) their signaling pathways. Antisense oligos will be used in cell culture to elucidate the pathways linked to each receptor subtype. Evidence for a novel receptor will lead to an effort to clone the new receptor. Finally, 5) studies of the effects of NPY on neointimal proliferation in rat carotid artery will be used to test the hypothesis that injury is associated with up-regulation of the NPY system in the vessel and that treatment with antagonists will reverse these effects. These studies will lead to information useful in developing new anti-mitogenic therapies.