Regulation of angiogenic inhibitors in cardiac remodeling and hypertrophy

Doctor's Name: 
Susan Crawford, MD
Children's Memorial Hospital, Chicago, IL

The aim of this grant proposal is to study growth factors and inhibitors of angiogenesis (i.e., blood vessel growth). Regulation of blood vessel growth is critical to normal fetal cardiac development and the amount of neovascularization is held in check by naturally occurring inhibitors of angiogenesis. Loss of one of the endogenous inhibitor proteins contributes to pathologic cardiac remodeling and hypertrophy. Dr. Crawford's group has discovered one of these natural inhibitors that is to date the first hypoxia-regulated inhibitors. She now wants to study this inhibitor protein further in genetically engineered mice that are deficient in another inhibitor that causes a clinical spectrum of dilated cardiomyopathy, ventricular hypertrophy and increased angiogenesis of intramyocardial vessels. The second portion of the study is to assess the involvement of these inhibitor proteins in 50 hearts of patients with dilated cardiomyopathy in the Farouk Idriss Cardiac Pathology registry at Children's Memorial Hospital. If it can be proven that loss of these inhibitors contributes to pathologic cardiac remodeling and hypertrophy, then pharmacological replacement may help restore the balance of these mediators, reverse the pathology, and improve cardiac function.

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