ESTROGEN INDUCED PROTEINS IN VASCULAR SMOOTH MUSCLE

铁在心血管疾病中起关键作用：血管平滑肌的增殖和迁移。我们已经分离、合成并完成了由结核分枝杆菌分泌的铁螯合剂家族的极具前景的中试研究。它们阻断氧化还原反应，在螯合剂中是独一无二的，因为它们是脂溶性的，这一特性使它们能够迅速进入细胞，并在极低浓度下具有生理活性。体外螯合素可抑制体外培养的人血管平滑肌细胞（VSMC）的增殖。我们建议阐明铁与脂溶性外螯合蛋白螯合抑制VSMC生长的分子机制。在培养的人类VSMCs中，我们将验证外切蛋白通过抑制细胞周期蛋白依赖性激酶的活性，在G1和S期阻断细胞周期进程的假设。我们认为这是通过抑制蛋白的上调而发生的。我们将研究外螯素在人类VSMC中的摄取和细胞内分布。

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.