"Half-baked" Analysis: Hepcidin's role in atherosclerosis
This practice grant was written several years ago so I apologize if any of the science is out of date.
The grant can be found here: Download word document
Abstract:
Iron has long been hypothesized to play a role in heart disease, but both a potential mechanism and experimental evidence have been lacking. Recently, progress has been made on both of these fronts, and the current thinking is that iron accumulation in macrophages leads to the formation of foamy macrophages, an important step in atherogenesis. This is an exciting finding because it may lead to new strategies to prevent heart disease. For example, one way to decrease iron load in macrophages would be to lower hepcidin levels. And in fact, this has been done in a mouse model with promising results. However, lowering hepcidin levels by altering BMP signaling has several effects on the body, not the least of which is increasing circulating iron levels, and therefore it cannot be definitely determined how hepcidin lowered atherogenesis in this mouse model, and one also must question the feasibility of translating this finding to human patients. This grant seeks to clarify hepcidin’s role in atherogenesis by using a mouse model to directly alter hepcidin’s cellular target, ferroportin, in macrophages, thereby eliminating any off target effects of hepcidin.