DOI: 10.1161/circ.148.suppl_1.15077 ISSN: 0009-7322

Abstract 15077: Mitochondrial LonP1 Upregulation in End Stage Heart Failure

Saifullah Soliman, Ayman Maher M Ibrahim, Dr. Kerolos Wagdy, Peter Selwanos, Hadir Khedr, SABER MOSTAFA MOSTAFA, Ajay M Shah, Magdi Yacoub, Yasmine Aguib
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Mitochondrial dysfunction is a hallmark of heart failure (HF), where correct mitochondrial proteins’ folding is challenged under mitochondrial stress. To restore mitochondrial proteostasis and homeostasis, the mitochondrial unfolded protein response (UPR mt ) is activated, a mechanism not fully elucidated in HF.

Purpose: We here investigate the UPR mt induction in advanced/end-stage HF patients requiring Left Ventricular Assist Device (LVAD). In addition, we analyzed the potential influence on clinical outcome.

Methods: RNA was extracted from 44 Left Ventricular discs excised during implantation of LVAD from end-stage HF patients and from 5 control LV tissues. Quantitative PCR was performed to assess the relative expression levels of UPR mt machinery ( ATF5, CHOP, mtDNAj, HSP60/10, CLpP and LonP1 ). Immunoblotting was performed to validate mRNA levels. LonP1 subgrouping was performed in reference to LVAD patients’ 3 rd quartile of pre-LVAD Lonp1 mRNA levels. The primary outcome for the Kaplan-Meier survival analysis was all-cause mortality post-LVAD intervention.

Results: Gene expression analysis revealed a significant increase in mRNA levels of CHOP and LonP1. Immunoblotting validated the upregulation of CHOP & LonP1 in end-stage HF tissue in comparison to controls. In High-LonP1 patients, we observed a significant increase in left ventricular ejection fraction and blood sodium levels while serum levels of ST-2 and blood urea levels were significantly decreased. High-LonP1 patients had a significantly higher probability of survival post-LVAD intervention and potential to recover myocardial function.

Conclusion: This study suggests LonP1 as a potential marker of myocardial recovery and clinical outcome in end-stage heart failure patients treated by LVADs.

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