Abstract 20284: Cardiac Ankyrin Repeat Protein Expression Is Impacted By Ventricular Loading Conditions In Chronic Heart Failure
Introduction: Ankyrin repeat domain 1 (ANKRD1), the gene encoding CARP, a transcription co-factor that translocates to the nucleus in response to mechanical stretch, is up-regulated in heart failure (HF). Left Ventricular Assist Devices (LVADs) for end-stage HF unloads the ventricle and reduces wall stress and wall stretch, and could have a direct impact on ANKRD1 expression.
Hypothesis: LVAD support will lead to decreased expression of ANKRD1 in heart.
Methods: Left ventricular (LV) apical core specimens were acquired at the time of LVAD implantation (pre-LVAD HF samples). LV tissue was also obtained from explanted hearts of patients undergoing heart transplantation at the Ohio State University (post-LVAD samples). Approval for use of human subjects was obtained from the IRB. LV tissue from healthy donor hearts not suitable for transplantation was obtained through Lifeline of Ohio (control non-failure samples). Patients who received LVAD support and had a subsequent transplantation (pre- and post-LVAD samples) were used for the analysis. Tissue lysates were made from LV samples and immunoblots for protein expression were performed using standard laboratory techniques.
Results: 6 paired samples (pre- and post-LVAD) were analyzed and compared to control non-failing (NF) LV samples. All LVAD patients had an ejection fraction <20%, and there was an equal proportion of ischemic and non-ischemic LV samples. ANKRD1 expression prior to LVAD support (pre-LVAD HF) was increased by nearly 50% (Figure 1, p<0.05) when compared to NF hearts. Notably, after LVAD support (post-LVAD HF) ANKRD1 levels decreased significantly (Figure 1, p<0.05) and were similar to NF levels.
Conclusions: ANKRD1 protein expression decreases after LVAD support and has the potential to be a biomarker to assess hemodynamic loading conditions and overall response to LVAD therapy.
Author Disclosures: A. Kempton: None. B. Canan: None. F. Kline: None. P. Janssen: None. P.J. Mohler: None. S.A. Smith: Consultant/Advisory Board; Modest; Relypsa.
- © 2016 by American Heart Association, Inc.