ESTROGEN INDUCED PROTEINS IN VASCULAR SMOOTH MUSCLE

铁在心血管疾病中起着关键作用：血管平滑肌增殖和迁移。 我们已经分离，合成和完成了非常有前途的试点研究家庭的铁螯合剂，exochenins分泌的结核分枝杆菌。 它们阻断氧化还原反应，并且在螯合剂中是独特的，因为它们是脂溶性的，这是一种允许它们快速进入细胞并在极低浓度下具有生理活性的性质。 在去铁形式中，外螯素防止培养的人血管平滑肌细胞（VSMC）的增殖。 我们建议阐明铁螯合与脂溶性exochelins阻止VSMC生长的分子机制。 在培养的人VSMCs中，我们将测试外螯素通过抑制细胞周期蛋白依赖性激酶的活性在G1和S期阻断细胞周期进展的假设。 我们认为这是通过上调抑制蛋白发生的。 我们将研究摄取和细胞内分布的外螯素在humjan VSMC。

Iron plays a critical role in cardiovascular diseases: vascular smooth muscle proliferation and migration. We have isolated, synthesized and completed highly promising pilot studies on a family of iron chelators, exochenins secreted by Mycobacterium tuberculosis. They block redox reactions and are unique among chelators in that they are lipid soluble, a property that permits them to rapidly enter cells and be physiologically active at extremely low concentrations. In the desferri-form, exochelins prevent proliferation of cultured human vascular smooth muscle cells (VSMC). We propose to elucidate the molecular mechanism by which iron chelation with lipid soluble exochelins prevent VSMC growth. In cultured humans VSMCs, we will test the hypothesis that exochelins block progression through the cell cycle at both the G1 and S phases by inhibiting activity of cyclin-dependent kinases. We propose that his occurs through upregulation of inhibitory proteins. We will examine the uptake and intracellular distribution of exochelins in humjan VSMC.