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.
|Kulik, T J; Alvarado, S P (1993) Effect of stretch on growth and collagen synthesis in cultured rat and lamb pulmonary arterial smooth muscle cells. J Cell Physiol 157:615-24|
|Bialecki, R A; Kulik, T J; Colucci, W S (1992) Stretching increases calcium influx and efflux in cultured pulmonary arterial smooth muscle cells. Am J Physiol 263:L602-6|
|Kulik, T J; Bialecki, R A; Colucci, W S et al. (1991) Stretch increases inositol trisphosphate and inositol tetrakisphosphate in cultured pulmonary vascular smooth muscle cells. Biochem Biophys Res Commun 180:982-7|