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

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Abstract

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.

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Change history

  • 02 August 2017

    An erratum to this article has been published.

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Acknowledgements

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

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Correspondence to Zhongjun J. Wu.

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The authors declare that they have no conflict of interest.

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The original version of this article was revised. The second author’s name was misspelt. The correct name is updated in the article.

An erratum to this article is available at https://doi.org/10.1007/s11010-017-3126-6.

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Mondal, N.K., Li, T., Chen, Z. et al. Mechanistic insight of platelet apoptosis leading to non-surgical bleeding among heart failure patients supported by continuous-flow left ventricular assist devices. Mol Cell Biochem 433, 125–137 (2017). https://doi.org/10.1007/s11010-017-3021-1

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Keywords

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