Many diseases including hypertension and atherosclerosis are characterized by aberrant vascular cell growth. Understanding the mechanisms regulating vascular growth will facilitate the development of treatment that will either suppress or enhance pathological vascular cell growth. Many diseases again including hypertension are also associated with aberrant regulation of vascular function. The studies described in this proposal evaluate how interactions between sympathetic neurons, EC and VSM regulate vascular growth and function and will add significantly to our understanding of physiological and pathological vascular regulatory mechanisms. This understanding may facilitate the treatment or prevention of cardiovascular disease. It is well known that the sympathetic nervous system regulates the growth and development of the vasculature as well as vascular contractile function. The mechanisms of this regulation are not fully understood. The overall hypothesis of this proposal is that the sympathetic nervous system interacts with vascular cells to regulate vascular cell growth and function via catecholamine-dependent and catecholamine-independent mechanisms. The first two specific aims consider how sympathetic/vascular cell interactions regulate vascular cell growth. In vitro methodology will be used to characterize sympathetic/vascular cell interactions that regulate vascular cell growth. The roles of cell-to-cell contact and reciprocal exchange of secreted products will be considered. The roles of catecholamines, synaptic release and peptide growth factors will also be evaluated. The last two specific aims consider how catecholamines interact with two vascular-derived vasoactive mitogens (platelet-derived growth factor and fibroblast growth factor) in vivo. Molecular biological techniques will be used to assess modulation of induction of aortic gene expression. Intravital microscopy will be used to assess control of microvessel diameter. Regulation of arterial blood pressure will also be studied.
| Damon, Deborah H (2005) Sympathetic innervation promotes vascular smooth muscle differentiation. Am J Physiol Heart Circ Physiol 288:H2785-91 |
| Gonzalez, W; Chen, Z; Damon, D H (2001) Transforming growth factor-beta regulation of endothelin expression in rat vascular cell and organ cultures. J Cardiovasc Pharmacol 37:219-26 |
| Damon, D H (2001) PC12 cells stimulate vascular smooth muscle growth. J Cardiovasc Pharmacol 38:625-32 |
| Damon, D H (2000) VSM growth is stimulated in sympathetic neuron/VSM cocultures: role of TGF-beta2 and endothelin. Am J Physiol Heart Circ Physiol 278:H404-11 |
| Damon, D H (2000) Adrenoceptor-mediated modulation of endothelial-dependent vascular smooth muscle growth. J Auton Pharmacol 20:47-54 |
| Damon, D H (1998) Postganglionic sympathetic neurons express endothelin. Am J Physiol 274:R873-8 |
| Lange, D L; Damon, D H (1997) Transforming growth factor beta constricts rat cremaster arterioles. Microvasc Res 54:81-7 |
