This is a competitive renewal application seeking funds to support a Program Project Grant at the Oregon Health & Science University. The Program is composed of five interwoven projects designed to test the umbrella hypothesis that stressors of the fetal cardiovascular and renal systems irreversibly alter early gene expression patterns and thereby predispose the offspring for disease in later life. Project by Woods will investigate the role of gender in determining susceptibility to hypertension after intrauterine protein deprivation. Project by Faber will study the role of prenatal of role of prenatal angiotensin II and hypertension in setting long-term blood presume in adults as well as renal and cardiac function. Project by Thornburg will investigate the relationship between cardiac myocyte and coronary vascular development and their long-term effects on disease susceptibility. Project by Baby will investigate the role of protein deprivation in determining long-term kidney function and regulation of the renin-angiotensin system. Project by Stork will investigate the role of the mitogen-activate protein kinase system as a regulator of cell proliferation and cell growth during the development. Core A is the administrative core that will oversee the administration of the program grant and provide coordination services. Core B is the animal core, headed by a senior veterinarian who oversee animal purchase and use and will provide overall cost savings. Core C is the imaging core and is headed by the director of OHSU Anatomic Pathology. It will provide immunochemistry histology and sophisticated microscopy services. This program has attracted a highly talented interdisciplinary faculty and the program is designed to integrated whole animal physiology cell culture, transgenic animals, and molecular biology to address problems of high-priority in the development of human disease.
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