Targeting myocyte gangliosides for cardioprotection

Chronic kidney disease (CKD) is a growing epidemic due to an increase in the aging population. CKD patients have a risk of reaching end-stage kidney failure which requires these patients to receive dialysis or a kidney transplant. These patients are further plagued by co-morbidities such as heart failure, hypertension, and diabetes due to the active progression of the disease. Sudden cardiac death from abnormal heart rhythm is the most common cause of death among patients with CKD. This is mostly due to overgrowth of the heart, called cardiac hypertrophy. There have been many attempts to prevent hypertrophic growth from occurring in the heart of CKD patients and various possible treatments have been studied. Our lab has identified a hormone produced in the kidney that protects the heart from overgrowth called klotho. Our lab believes that patients with failing kidneys lose the ability to produce this hormone thus causing these patients to have a higher chance of developing heart failure. We have shown the lack or decrease of this hormone is an important cause of heart overgrowth and sudden death in CKD patients. Though we have attempted to mass-produce this hormone, our efforts to produce large quantities have yet to be feasible. This thesis project aims to investigate different methods in protecting the hearts of CKD patients. We have highlighted that this project helps to further understand how the kidney hormone protects the heart from overgrowth. Thereby, leading to new potential treatments for CKD patients afflicted by heart failure.