Platelet-Monocyte Aggregates and C-Reactive Protein are Associated with VTE in Older Surgical Patients

Shih, Lauren; Kaplan, David; Kraiss, Larry W.; Casper, T. Charles; Pendleton, Robert C.; Peters, Christopher L.; Supiano, Mark A.; Zimmerman, Guy A.; Weyrich, Andrew S.; Rondina, Matthew T.

doi:10.1038/srep27478

Cited by 24 publications

(25 citation statements)

References 35 publications

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“…A study suggested that monocyte-related in ammatory mechanisms may be involved in the pathophysiological processes of VTE [17] . Monocytes, platelet aggregation, and C-reactive protein are associated with VTE [18] , which supports the conclusion that VTE is associated with in ammation. GO enrichment analysis found that DEGs are mainly involved in the composition of ribosomes in the cytoplasm.…”

Section: Discussionsupporting

confidence: 83%

Immunological Analysis and Differential Genes Screening of Venous Thromboembolism

Gao

Xie

et al. 2020

Preprint

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Purpose: To explore the pathogenesis of venous thromboembolism (VTE) and provide bioinformatics basis for the prevention and treatment of VTE. Methods: The R software was used to obtain the gene expression profile data of GSE19151, combining with the CIBERSORT database, obtain immune cells and differentially expressed genes (DEGs) of blood samples of VTE patients and normal control, and analyze DEGs for GO analysis and KEGG pathway enrichment analysis. Then, the protein-protein interaction (PPI) network was constructed by using the STRING database, the key genes (hub genes) and immune differential genes were screened by Cytoscape software, and the transcription factors (TFs) regulating hub genes and immune differential genes were analyzed by the NetworkAnalyst database. Results: Compared with the normal group, monocytes and resting mast cells were significantly expressed in the VTE group, while regulatory T cells were significantly lower. Ribosomes were closely related to the occurrence of VTE. 10 hub genes and immune differential genes were highly expressed in VTE. MYC, SOX2, XRN2, E2F1, SPI1, CREM and CREB1 can regulate the expressions of hub genes and immune differential genes. Conclusions: Ribosomal protein family genes are most relevant to the occurrence and development of VTE, and the immune differential genes may be the key molecules of VTE, which provides new ideas for further explore the pathogenesis of VTE.

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Section: Discussionsupporting

confidence: 83%

Immunological Analysis and Differential Genes Screening of Venous Thromboembolism

Gao

Xie

et al. 2020

Preprint

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“…The expression of monocyte surface markers, platelet surface adhesion molecules (e.g. P-selectin), and platelet-monocyte aggregation (PMAs) was evaluated by flow cytometry 13, 18–20 . All antibodies were from BD Biosciences.…”

Section: Methodsmentioning

confidence: 99%

Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging

Campbell

Franks

Bhatnagar

et al. 2018

The Journal of Immunology

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Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream cytokine synthesis in aging remains poorly understood. Platelets and monocytes were isolated from healthy younger (age <45, = 37) and older (age ≥65, = 30) adults and incubated together under autologous and nonautologous conditions. Synthesis of inflammatory cytokines by monocytes, alone or in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (41 ± 5 versus 9 ± 2 ng/ml, < 0.0001) and MCP-1 (867 ± 150 versus 216 ± 36 ng/ml, < 0.0001) than younger adults. Platelets from older adults were sufficient for upregulating the synthesis of inflammatory cytokines by monocytes. Using RNA-sequencing of platelets followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, increases with aging (∼9-fold versus younger adults, < 0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced excessive IL-8 and MCP-1 synthesis in aging to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls the synthesis of inflammatory cytokines by monocytes. Alterations in the platelet molecular signature and signaling to monocytes may contribute to dysregulated inflammatory syndromes in older adults.

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“…As part of the primary study protocol, 8 comprehensive bilateral, lower extremity duplex compression ultrasonography (CUS) was performed by registered vascular technologists for all patients approximately 2 to 3 days after surgery. A second, follow-up CUS was also performed about 14 days postoperatively.…”

Section: Methodsmentioning

confidence: 99%

Postoperative Changes in the Systemic Inflammatory Milieu in Older Surgical Patients

Shih

Güler

Syed

et al. 2017

Clin Appl Thromb Hemost

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Dysregulated inflammation is a central component of wound healing following surgery. We prospectively enrolled older patients (n ¼ 25, age 65 + 7 years) undergoing elective total knee arthroplasty or total hip arthroplasty secondary to advanced osteoarthritis (OA) and healthy controls (n ¼ 48). Inflammatory, proangiogenic (vascular endothelial growth factor [VEGF], monocyte chemoattractant protein-1 [MCP-1], and interleukin-8 [IL-8]), and antiangiogenic (interferon g [IFN-g] and IL-4) factors were measured using a high-sensitivity biochip. Patients with OA had significantly higher baseline VEGF (10.5 + 1.2 pg/mL vs 4.8 + 0.2 pg/mL, P < .001), MCP-1 (130.6 + 7.7 pg/mL vs 88.6 + 3.9 pg/mL, P < .0001), and IL-8 (4.0 + 0.5 pg/mL vs 2.6 + 0.1 pg/mL, P < .05). Postoperatively, the levels of VEGF (10.5 + 1.2 pg/mL vs 18.8 + 1.5 pg/mL, P < .001) and MCP-1 (130.6 + 7.7 pg/mL vs 153.1 + 11.5 pg/mL, P < .05) increased significantly. Baseline and postoperative MCP-1 levels correlated positively and significantly with age. The levels of IFN-g and IL-4 (which has anti-inflammatory properties) did not significantly differ at baseline in patients with OA compared to controls and did not significantly rise postoperatively. We conclude that systemic levels of proinflammatory and angiogenic proteins are increased in patients with OA and rise further postoperatively, while proteins that restrain inflammation and angiogenesis do not coordinately rise. These findings implicate imbalance in inflammatory pathways in OA that may contribute to its pathobiology.

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Platelet-Monocyte Aggregates and C-Reactive Protein are Associated with VTE in Older Surgical Patients

Cited by 24 publications

References 35 publications

Immunological Analysis and Differential Genes Screening of Venous Thromboembolism

Immunological Analysis and Differential Genes Screening of Venous Thromboembolism

Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging

Postoperative Changes in the Systemic Inflammatory Milieu in Older Surgical Patients

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