Mechanistic insight of platelet apoptosis leading to non-surgical bleeding among heart failure patients supported by continuous-flow left ventricular assist devices.
Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference). Production of reactive oxygen species (ROS) in platelets, total antioxidant capacity (TAC), oxidized low-density lipoproteins (oxLDL), expression of Bcl-2 and Bcl-xL, Bax and release of cytochrome c (Cyt.c), platelet mitochondrial membrane potential (Δψm), activation of caspases, gelsolin cleavage and platelet apoptosis were examined. Significantly elevated ROS, oxLDL and depleted TAC were evident in the bleeder group compared to non-bleeder group (p < 0.05). Platelet pro-survival proteins (Bcl-2, Bcl-xL) were significantly reduced in the bleeder group in comparison to the non-bleeder group (p < 0.05). Translocation of Bax into platelet mitochondria membrane and subsequent release of Cyt.c were more prevalent in the bleeder group. Platelet mitochondrial damage, activation of caspases, gelsolin cleavage, and ultimate platelet apoptosis in the bleeder group were observed. Oxidative stress and activation of both intrinsic and extrinsic pathways of platelet apoptosis may be linked to NSB in CF-LVAD patients. Additionally, biomarkers of oxidative stress, examination of pro-survivals and pro-apoptotic proteins in platelets, mitochondrial damage, caspase activation, and platelet apoptosis may be used to help identify HF patients at high risk of NSB post-implant.
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA.|Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, Baltimore, MD, 21201, USA.
Nandan K
NK
Mondal
Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, Baltimore, MD, 21201, USA.
Tieluo
T
Li
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA.
Zengsheng
Z
Chen
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Hegang H
HH
Chen
Department of Clinical Engineering, University of Maryland Medical Center, Baltimore, MD, USA.
Erik N
EN
Sorensen
Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, Baltimore, MD, 21201, USA.
Si M
SM
Pham
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA.
Michael A
MA
Sobieski
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA.
Steven C
SC
Koenig
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA.
Mark S
MS
Slaughter
Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, Baltimore, MD, 21201, USA.
Bartley P
BP
Griffith
Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, USA. zwu@som.umaryland.edu.|Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, Baltimore, MD, 21201, USA. zwu@som.umaryland.edu.
Zhongjun J
ZJ
Wu
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000628:therapy; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
Cardiac failure; Clinical complication; Mechanical circulatory support device; Signaling in platelet apoptosis