The candidate, Dr. Detlef Wencker, Assistant Professor of Medicine, joined the Section of CardiovascularMedicine and Heart Failurerfransplant Program at Yale University in order to carry on his past researchendeavors with the long-term goal of becoming an independent investigator. In extension of his prior work,he has chosen to investigate the basic mechanism of heart failure (CHF) in humans in order to find newtreatment modalities that target the cellular origin of the disease. Yale University with its outstanding clinicaland basic science research environment combined with a highly effective mentorship by Dr. Stuart Katzplaces the candidate in a strong position to accomplish this task. This award will allow the candidate tocontinue his research career development by obtaining a Masters in Public Health in Biostatistics and byconsolidating his knowledge of both clinical and basic science. The proposed research seeks to identify the role of apoptosis in decompensating CHF among patientswith end-stage dilated cardiomyopathy. Preliminary data suggest that skeletal muscle apoptosis isupregulated during acute CHF exacerbation.
Aim 1 will investigate the hypothesis that myocyte apoptosis ofthe skeletal muscle undergoes a dynamic process from stable, compensated CHF to acute cardiacdecompensation.
The second aim hypothesizes that the dynamics of apoptosis in the skeletal muscleparallels that in the heart. The candidate will monitor the rate of apoptosis, the level of pro-apoptoticinflammatory cytokines and the state of apoptotic regulators in skeletal and cardiac muscle specimens ofCHF patients longitudinally at times of compensation and times of acute CHF exacerbation.
Specific aim 3 will examine if treatment with erythropoietin, a glycoprotein with potent anti-apoptotic properties, of patientswith moderate to severe CHF will prevent myocyte cell loss and therefore delay the development ofdecompensated CHF. The results generated will yield critical insights into the role of skeletal and cardiac muscle apoptosisduring acute CHF decompensation. These data have the potential to translate into more effective, clinicallyrelevant CHF treatments.
