Khadija Rafiq, PhD

Cardiovascular disease, including heart failure, is the major cause of death in patients with diabetes. A contributing factor to heart failure in such patients is the development of diabetic cardiomyopathy. Several advances in the treatment of patients with diabetic cardiomyopathy have improved survival. However, this disease process is still pre-eminent in affecting the morbidity and mortality of patients with diabetes.

The research goal in the laboratory is to study the molecular and cellular mechanisms involved in myocardial cell death.  Inflammatory cells and their proteases are considered a key element that orchestrate myocardial repair.  Although beneficial at early stages, inflammatory proteases may contribute to myocyte death and subsequent alterations in both the geometry and mechanical properties of the heart.  Using intact tissue and cell culture models, my laboratory’s research interest focus on elucidating the role of inflammatory serine proteases in the development of diabetic cardiomyopathy. It is well known that inflammation plays a role in the development of diabetic cardiomyopathy. However, in all these studies the action of inflammatory pathways has focused on action of oxidative stress or cytokines/chemokines and their role in myocyte growth and extracellular matrix remodeling during the development of diabetic cardiomyopathy. My laboratory suggests a novel mechanism for entry into pathways that modulate IR/IGF-1R signaling and myocyte dysfunction by inflammatory serine proteases. IR/IGF-1R signaling is anticipated to assume importance in maintaining myocyte metabolism and survival and in increasing myocardial protection in response to ischemia or ischemia reperfusion injury. Current therapies with insulin or IGF-1 administration have been shown to restore IR/IGF-1R signaling and to offer cardio-protection. However, excessive or inappropriate use of these therapies has been shown to increase the risk of cardiovascular diseases in diabetic patients. Therefore, my lab tests the effectiveness of inflammatory serine proteases blockade therapy in preventing/attenuating IR/IGF-1R signaling downregulation and protecting the myocardium during the development of diabetic cardiomyopathy.

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