NEUROPEPTIDE Y RECEPTORS AND VASCULAR REMODELING

描述：伴随着血管的增殖和凋亡。 高血压和动脉粥样硬化中发生的重塑。而当 众所周知，交感神经是营养的，促有丝分裂的作用 儿茶酚胺很弱。目前的假设是神经肽Y 这些神经中的(NPY)共递质是参与 血管平滑肌生长。提供的初步数据表明， NPY刺激生长和细胞凋亡。其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 神经肽Y的作用及其对有丝分裂和细胞凋亡平衡的理解 2)研究神经肽Y代谢酶的调节作用。 与增长效应的关联性，以此作为了解 这些酶可能参与调节生长而不是抑制生长。 影响；3)确定受体的亚型；4)它们的信号 小路。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联的通路。一种新受体的证据 将导致克隆新受体的努力。最后，5)研究 神经肽Y对大鼠颈动脉新生内膜增殖的影响 用来检验这样一种假设，即损伤与上调有关 血管内NPY系统和拮抗剂治疗将 逆转这些影响。这些研究将带来有用的信息 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.