Grant: Operating Grant

Marfan syndrome (MFS) is a genetic disease of the connective tissue, which provides material and support for our skeleton, muscles, blood vessels and other parts of our bodies. People may be tall and thin with slender, tapering fingers, long arms and legs, and spine curvature. They often have heart and eye problems. In some patients, the condition is very mild and the person has few or no symptoms. Others are always at risk of life-threatening problems, which usually involve damage to the valves in the heart or weakening of the large blood vessels leading from the heart (e.g. aorta). If the blood vessels become weak, they can balloon out (dilate) and break (rupture), which might cause the person to die suddenly. We have only a limited ability to stop the progression of disease in Marfan syndrome. Typically we use medicines that lower heart rate or blood pressure (or both). But this does not prevent the disease and very few drugs work well enough to keep patients from needing surgery or dying suddenly because a blood vessel has torn open. Our objective is to understand intra and extra cellular events within the walls of the blood vessels that occur during the early stage of disease using a well-established mouse model of Marfan syndrome that mimics human disease. Our previous findings using the mouse model have shown that a blood lowering drug called Losartan improves the blood vessel function and delay the dilatation of the blood vessel. We would like to understand the mechanism underlying such effects. We also intend to find new indicators of disease progression in blood samples of human subjects and MFS mice in both treated and non-treated groups. This study will help us to find better ways to treat people with Marfan syndrome and find early indicators (bio-markers) as a tool to detect early changes in blood vessels. If we can do this, fewer people will need emergency surgery for torn blood vessels and fewer will die suddenly.