STRETCH AS A GROWTH STIMULUS IN VASCULAR SMOOTH MUSCLE

平滑肌的异常生长在肺血管中起重要作用 疾病，它是不知道是什么调制它，但两者的临床 实验观察表明，机械刺激可能 发挥重要作用。 我提议检验这个假设， 牵张可调节肺组织生长和蛋白质合成 血管平滑肌细胞 我会用培养的细胞 确定拉伸是否刺激增生或 肥厚 拉伸对整体蛋白质合成的影响， 以及对特定蛋白质的影响。 如果像 预期，拉伸确实具有生理效应，其 机制将被研究，细胞内的“信号”与 增长是调查的最初重点。 最终目标 是在分子水平上理解机械刺激如何影响 平滑肌细胞 这个项目将为我打下良好的分子基础 生物学：它需要集中在几个基本方面 分子生物学，需要集中在几个 分子生物学的基本方面和经验，在许多 重要的实验技术。 Nadal-Ginard博士的经验 清晰和批判性的思维对我来说是无价的， 科学成熟。 最后，在实验室中， 拟议的项目将进行的是装备精良，非常 活跃的，有一个“临界质量”的调查人员感兴趣的许多 分子和细胞生物学方面。

Abnormal growth of smooth muscle is important in pulmonary vascular disease, and it is not known what modulates it, but both clinical and experimental observations suggest that mechanical stimuli may play an important role. I propose to examine the hypothesis that stretch acts to modulate growth and protein synthesis in pulmonary vascular smooth muscle cells. I will use cultured cells to determine whether stretch stimulates either hyperplasia or hypertrophy. The effect of stretch on overall protein synthesis, as well as on specific protein will be determined. If, as anticipated, stretch does have a physiological effect(s), its mechanisms will be studied, with intracellular "signal" linked with growth being the initial focus of investigation. The ultimate goal is to understand on a molecular level how mechanical stimuli affect smooth muscle cells. This project should afford me an excellent grounding in molecular biology: It requires concentration in several fundamental aspects of molecular biology and requires concentration in several fundamental aspects of molecular biology and experience in many important experimental techniques. Dr. Nadal-Ginard's experience and clear and critical thinking should be invaluable in helping me mature scientifically. Finally, the laboratory in which the proposed project will be undertaken is well equipped and very active, with a "critical mass" of investigators interested in many aspects of molecular and cellular biology.