Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading
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 unlo...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-10-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2020.1714573 |
| _version_ | 1797684222529372160 |
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| author | Callie Frey Antigoni G. Koliopoulou Emilie Montenont Neal D. Tolley Hadi Javan Stephen H. McKellar Stavros G. Drakos Craig H. Selzman Matthew T. Rondina |
| author_facet | Callie Frey Antigoni G. Koliopoulou Emilie Montenont Neal D. Tolley Hadi Javan Stephen H. McKellar Stavros G. Drakos Craig H. Selzman Matthew T. Rondina |
| author_sort | Callie Frey |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:26:33Z |
| format | Article |
| id | doaj.art-bd8de728c0ce49a79e01b27e4193bbde |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:26:33Z |
| publishDate | 2020-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-bd8de728c0ce49a79e01b27e4193bbde2023-09-15T10:32:03ZengTaylor & Francis GroupPlatelets0953-71041369-16352020-10-0131795295910.1080/09537104.2020.17145731714573Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloadingCallie Frey0Antigoni G. Koliopoulou1Emilie Montenont2Neal D. Tolley3Hadi Javan4Stephen H. McKellar5Stavros G. Drakos6Craig H. Selzman7Matthew T. Rondina8University of Utah Molecular Medicine ProgramUniversity of UtahUniversity of Utah Molecular Medicine ProgramUniversity of Utah Molecular Medicine ProgramUniversity of UtahUniversity of UtahUniversity of Utah Molecular Medicine ProgramUniversity of Utah Molecular Medicine ProgramUniversity of Utah Molecular Medicine ProgramPatients 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.http://dx.doi.org/10.1080/09537104.2020.1714573heart failureleft ventricular assist deviceplateletsrnatranscriptome |
| spellingShingle | Callie Frey Antigoni G. Koliopoulou Emilie Montenont Neal D. Tolley Hadi Javan Stephen H. McKellar Stavros G. Drakos Craig H. Selzman Matthew T. Rondina Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading Platelets heart failure left ventricular assist device platelets rna transcriptome |
| title | Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| title_full | Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| title_fullStr | Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| title_full_unstemmed | Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| title_short | Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| title_sort | longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading |
| topic | heart failure left ventricular assist device platelets rna transcriptome |
| url | http://dx.doi.org/10.1080/09537104.2020.1714573 |
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