Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability

Aisling M Rehill; Gemma Leon; Sean McCluskey; Ingmar Schoen; Yasmina Hernandez-Santana; Stephanie Annett; Paula Klavina; Tracy Robson; Annie M Curtis; Thomas Renné; Seamus Hussey; James S O'Donnell; Patrick T Walsh; Roger J S Preston

doi:10.1016/j.jtha.2023.10.006

Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability

Standard

Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability. / Rehill, Aisling M; Leon, Gemma; McCluskey, Sean; Schoen, Ingmar; Hernandez-Santana, Yasmina; Annett, Stephanie; Klavina, Paula; Robson, Tracy; Curtis, Annie M; Renné, Thomas; Hussey, Seamus; O'Donnell, James S; Walsh, Patrick T; Preston, Roger J S.

in: J THROMB HAEMOST, Jahrgang 22, Nr. 2, 02.2024, S. 394-409.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rehill, AM, Leon, G, McCluskey, S, Schoen, I, Hernandez-Santana, Y, Annett, S, Klavina, P, Robson, T, Curtis, AM, Renné, T, Hussey, S, O'Donnell, JS, Walsh, PT & Preston, RJS 2024, 'Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability', J THROMB HAEMOST, Jg. 22, Nr. 2, S. 394-409. https://doi.org/10.1016/j.jtha.2023.10.006

APA

Rehill, A. M., Leon, G., McCluskey, S., Schoen, I., Hernandez-Santana, Y., Annett, S., Klavina, P., Robson, T., Curtis, A. M., Renné, T., Hussey, S., O'Donnell, J. S., Walsh, P. T., & Preston, R. J. S. (2024). Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability. J THROMB HAEMOST, 22(2), 394-409. https://doi.org/10.1016/j.jtha.2023.10.006

Vancouver

Rehill AM, Leon G, McCluskey S, Schoen I, Hernandez-Santana Y, Annett S et al. Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability. J THROMB HAEMOST. 2024 Feb;22(2):394-409. https://doi.org/10.1016/j.jtha.2023.10.006

Bibtex

@article{75958e9ec2e54e298ca9371a41cee262,

title = "Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability",

abstract = "BACKGROUND: Myeloid cell metabolic reprogramming is a hallmark of inflammatory disease; however, its role in inflammation-induced hypercoagulability is poorly understood.OBJECTIVES: We aimed to evaluate the role of inflammation-associated metabolic reprogramming in regulating blood coagulation.METHODS: We used novel myeloid cell-based global hemostasis assays and murine models of immunometabolic disease.RESULTS: Glycolysis was essential for enhanced activated myeloid cell tissue factor expression and decryption, driving increased cell-dependent thrombin generation in response to inflammatory challenge. Similarly, inhibition of glycolysis enhanced activated macrophage fibrinolytic activity through reduced plasminogen activator inhibitor 1 activity. Macrophage polarization or activation markedly increased endothelial protein C receptor (EPCR) expression on monocytes and macrophages, leading to increased myeloid cell-dependent protein C activation. Importantly, inflammation-dependent EPCR expression on tissue-resident macrophages was also observed in vivo. Adipose tissue macrophages from obese mice fed a high-fat diet exhibited significantly enhanced EPCR expression and activated protein C generation compared with macrophages isolated from the adipose tissue of healthy mice. Similarly, the induction of colitis in mice prompted infiltration of EPCR+ innate myeloid cells within inflamed colonic tissue that were absent from the intestinal tissue of healthy mice.CONCLUSION: Collectively, this study identifies immunometabolic regulation of myeloid cell hypercoagulability, opening new therapeutic possibilities for targeted mitigation of thromboinflammatory disease.",

author = "Rehill, {Aisling M} and Gemma Leon and Sean McCluskey and Ingmar Schoen and Yasmina Hernandez-Santana and Stephanie Annett and Paula Klavina and Tracy Robson and Curtis, {Annie M} and Thomas Renn{\'e} and Seamus Hussey and O'Donnell, {James S} and Walsh, {Patrick T} and Preston, {Roger J S}",

year = "2024",

month = feb,

doi = "10.1016/j.jtha.2023.10.006",

language = "English",

volume = "22",

pages = "394--409",

journal = "J THROMB HAEMOST",

issn = "1538-7933",

publisher = "Wiley-Blackwell",

number = "2",

}

RIS

TY - JOUR

T1 - Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability

AU - Rehill, Aisling M

AU - Leon, Gemma

AU - McCluskey, Sean

AU - Schoen, Ingmar

AU - Hernandez-Santana, Yasmina

AU - Annett, Stephanie

AU - Klavina, Paula

AU - Robson, Tracy

AU - Curtis, Annie M

AU - Renné, Thomas

AU - Hussey, Seamus

AU - O'Donnell, James S

AU - Walsh, Patrick T

AU - Preston, Roger J S

PY - 2024/2

Y1 - 2024/2

N2 - BACKGROUND: Myeloid cell metabolic reprogramming is a hallmark of inflammatory disease; however, its role in inflammation-induced hypercoagulability is poorly understood.OBJECTIVES: We aimed to evaluate the role of inflammation-associated metabolic reprogramming in regulating blood coagulation.METHODS: We used novel myeloid cell-based global hemostasis assays and murine models of immunometabolic disease.RESULTS: Glycolysis was essential for enhanced activated myeloid cell tissue factor expression and decryption, driving increased cell-dependent thrombin generation in response to inflammatory challenge. Similarly, inhibition of glycolysis enhanced activated macrophage fibrinolytic activity through reduced plasminogen activator inhibitor 1 activity. Macrophage polarization or activation markedly increased endothelial protein C receptor (EPCR) expression on monocytes and macrophages, leading to increased myeloid cell-dependent protein C activation. Importantly, inflammation-dependent EPCR expression on tissue-resident macrophages was also observed in vivo. Adipose tissue macrophages from obese mice fed a high-fat diet exhibited significantly enhanced EPCR expression and activated protein C generation compared with macrophages isolated from the adipose tissue of healthy mice. Similarly, the induction of colitis in mice prompted infiltration of EPCR+ innate myeloid cells within inflamed colonic tissue that were absent from the intestinal tissue of healthy mice.CONCLUSION: Collectively, this study identifies immunometabolic regulation of myeloid cell hypercoagulability, opening new therapeutic possibilities for targeted mitigation of thromboinflammatory disease.

AB - BACKGROUND: Myeloid cell metabolic reprogramming is a hallmark of inflammatory disease; however, its role in inflammation-induced hypercoagulability is poorly understood.OBJECTIVES: We aimed to evaluate the role of inflammation-associated metabolic reprogramming in regulating blood coagulation.METHODS: We used novel myeloid cell-based global hemostasis assays and murine models of immunometabolic disease.RESULTS: Glycolysis was essential for enhanced activated myeloid cell tissue factor expression and decryption, driving increased cell-dependent thrombin generation in response to inflammatory challenge. Similarly, inhibition of glycolysis enhanced activated macrophage fibrinolytic activity through reduced plasminogen activator inhibitor 1 activity. Macrophage polarization or activation markedly increased endothelial protein C receptor (EPCR) expression on monocytes and macrophages, leading to increased myeloid cell-dependent protein C activation. Importantly, inflammation-dependent EPCR expression on tissue-resident macrophages was also observed in vivo. Adipose tissue macrophages from obese mice fed a high-fat diet exhibited significantly enhanced EPCR expression and activated protein C generation compared with macrophages isolated from the adipose tissue of healthy mice. Similarly, the induction of colitis in mice prompted infiltration of EPCR+ innate myeloid cells within inflamed colonic tissue that were absent from the intestinal tissue of healthy mice.CONCLUSION: Collectively, this study identifies immunometabolic regulation of myeloid cell hypercoagulability, opening new therapeutic possibilities for targeted mitigation of thromboinflammatory disease.

U2 - 10.1016/j.jtha.2023.10.006

DO - 10.1016/j.jtha.2023.10.006

M3 - SCORING: Journal article

C2 - 37865288

VL - 22

SP - 394

EP - 409

JO - J THROMB HAEMOST

JF - J THROMB HAEMOST

SN - 1538-7933

IS - 2

ER -