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Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading

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posted on 2020-01-14, 13:35 authored by Callie Frey, Antigoni G. Koliopoulou, Emilie Montenont, Neal D. Tolley, Hadi Javan, Stephen H. McKellar, Stavros G. Drakos, Craig H. Selzman, Matthew T. Rondina

Patients with heart failure (HF) and left ventricular assist devices (LVAD) have dysregulated thrombo-inflammatory responses, mediated in part by platelets. While studies of platelet activation have been undertaken in HF, changes in the platelet transcriptome in HF patients following mechanical unloading with an LVAD have not been investigated. We prospectively enrolled and longitudinally followed advanced HF patients (n = 32) for a mean of 57 months post-LVAD implantation. For comparison, healthy donors were also enrolled (n = 20). Platelets were hyperactive in HF, as evidenced by significantly increased formation of circulating platelet-monocyte aggregate formation. Platelet transcriptome interrogation by next-generation RNA-sequencing identified that the expression of numerous genes (n = 588) was significantly (FDR < 0.05) altered in HF patients prior to LVAD implantation. Differentially expressed genes were predicted to have roles in angiogenesis, immune and inflammatory responses, apoptosis, and cardiac muscle contraction. 90 days following LVAD implantation, the majority (80%) of differentially expressed genes in HF patients normalized, as compared to the platelet transcriptomes of healthy donors. In conclusion, advanced HF is associated with marked alterations in the platelet transcriptome. While LVAD implantation to off load the failing heart results in resolution in the majority of differentially expressed genes, a subset of the platelet transcriptome remains persistently altered.

Funding

Funding Source: This work was supported by the NHLBI and NIA [HL142804, HL145237, HL130541, HL137606, AG059877, AG048022 to M.T.R.] and a VA Merit Award [I01 CX001696]. This material is the result of work supported with resources and the use of facilities at the George E. Wahlen VA Medical Center, Salt Lake City, Utah. Research reported in this publication was supported by the National Center for Research Resources of the National Institutes of Health under Award Number [U54 TR002355]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the University of Utah Flow Cytometry Facility in addition to the National Cancer Institute through Award Number [5P30CA042014-24]. The work was also supported by the Huntsman Cancer Institute High Throughput Genomics Shared Resource (HTG).

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