Molecular and Cellular Biochemistry

, Volume 433, Issue 1–2, pp 125–137 | Cite as

Mechanistic insight of platelet apoptosis leading to non-surgical bleeding among heart failure patients supported by continuous-flow left ventricular assist devices

  • Nandan K. Mondal
  • Tieluo Li
  • Zengsheng Chen
  • Hegang H. Chen
  • Erik N. Sorensen
  • Si M. Pham
  • Michael A. Sobieski
  • Steven C. Koenig
  • Mark S. Slaughter
  • Bartley P. Griffith
  • Zhongjun J. WuEmail author


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 (Δψ m), 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.


Cardiac failure Mechanical circulatory support device Clinical complication Signaling in platelet apoptosis 



The described research was sponsored by the National Institutes of Health (Grant 1R01HL124170).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Nandan K. Mondal
    • 1
    • 2
  • Tieluo Li
    • 2
  • Zengsheng Chen
    • 1
  • Hegang H. Chen
    • 3
  • Erik N. Sorensen
    • 4
  • Si M. Pham
    • 2
  • Michael A. Sobieski
    • 1
  • Steven C. Koenig
    • 1
  • Mark S. Slaughter
    • 1
  • Bartley P. Griffith
    • 2
  • Zhongjun J. Wu
    • 1
    • 2
    Email author
  1. 1.Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation InstituteUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Surgery, Artificial Organs LaboratoryUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Department of Epidemiology and Public HealthUniversity of Maryland School of MedicineBaltimoreUSA
  4. 4.Department of Clinical EngineeringUniversity of Maryland Medical CenterBaltimoreUSA

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