Enkhsaikhan Purevjav, MD, PhD
Effects of ACE Inhibitors and Beta-blockers on Cardiac Function in Murine Models of Inherited Dilated Cardiomyopathy due to Mutations in the Nebulette Gene
Baylor College of Medicine, Houston, TX
2008 Amount Awarded – $45,000
Dilated cardiomyopathy (DCM) is a serious disease of the heart muscle leading to congestive heart failure (CHF). Patients with CHF at the time of DCM diagnosis have a 4-fold hazard of death or transplantation in the first year after diagnosis compared to those without CHF. Therefore, early diagnosis and treatment of the "at risk" DCM population at the preclinical stages is crucial. The goal of this study is to find better ways to improve the clinical management and treatment of patients with DCM at the earliest stages of the disease. Classic cardiovascular therapy agents, such as, beta-adrenergic blockers and angiotensin converting enzyme (ACE) inhibitors are known to increase left ventricular function and reduce cardiac mortality in patients with CHF. This study will investigate the individual and combined effects of administering two common therapeutic agents, carvedilol (beta-blocker) and captopril (ACE inhibitor), during the preclinical and clinical stages of DCM in animal models with inherited DCM. The transgenic mice being studied carry human mutations in the nebulette gene. Cardiac function will be monitored during treatment. Then, to delineate the molecular mechanisms of carvedilol and/or captopril therapy, the mice hearts will be analyzed by histological, immunochemical, ultrastructural and protein analyses. This study will thus provide insight into the molecular mechanisms of the preventative and therapeutic effects of ACE inhibitors and beta-blockers on inherited human DCM.