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Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors

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Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors. / Gaspar, Renato Simões; Sage, Tanya; Little, Gemma; Kriek, Neline; Pula, Giordano; Gibbins, Jonathan M.

In: ANTIOXIDANTS-BASEL, Vol. 10, No. 3, 497, 23.03.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gaspar, RS, Sage, T, Little, G, Kriek, N, Pula, G & Gibbins, JM 2021, 'Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors', ANTIOXIDANTS-BASEL, vol. 10, no. 3, 497. https://doi.org/10.3390/antiox10030497

APA

Gaspar, R. S., Sage, T., Little, G., Kriek, N., Pula, G., & Gibbins, J. M. (2021). Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors. ANTIOXIDANTS-BASEL, 10(3), [497]. https://doi.org/10.3390/antiox10030497

Vancouver

Gaspar RS, Sage T, Little G, Kriek N, Pula G, Gibbins JM. Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors. ANTIOXIDANTS-BASEL. 2021 Mar 23;10(3). 497. https://doi.org/10.3390/antiox10030497

Bibtex

@article{69ca220ae2744401a4d62f4587f53e6a,
title = "Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors",
abstract = "BACKGROUND: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.OBJECTIVES: To establish whether PDI and Nox-1 cooperate to control platelet function.METHODS: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors.RESULTS: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1-/- platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals.CONCLUSIONS: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.",
keywords = "Metabolic syndrome, NADPH oxidase, Platelets, Protein disulphide isomerase, Redox biology",
author = "Gaspar, {Renato Sim{\~o}es} and Tanya Sage and Gemma Little and Neline Kriek and Giordano Pula and Gibbins, {Jonathan M}",
year = "2021",
month = mar,
day = "23",
doi = "10.3390/antiox10030497",
language = "English",
volume = "10",
journal = "ANTIOXIDANTS-BASEL",
issn = "2076-3921",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "3",

}

RIS

TY - JOUR

T1 - Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors

AU - Gaspar, Renato Simões

AU - Sage, Tanya

AU - Little, Gemma

AU - Kriek, Neline

AU - Pula, Giordano

AU - Gibbins, Jonathan M

PY - 2021/3/23

Y1 - 2021/3/23

N2 - BACKGROUND: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.OBJECTIVES: To establish whether PDI and Nox-1 cooperate to control platelet function.METHODS: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors.RESULTS: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1-/- platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals.CONCLUSIONS: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.

AB - BACKGROUND: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.OBJECTIVES: To establish whether PDI and Nox-1 cooperate to control platelet function.METHODS: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors.RESULTS: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1-/- platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals.CONCLUSIONS: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.

KW - Metabolic syndrome

KW - NADPH oxidase

KW - Platelets

KW - Protein disulphide isomerase

KW - Redox biology

UR - http://www.scopus.com/inward/record.url?scp=85102783704&partnerID=8YFLogxK

U2 - 10.3390/antiox10030497

DO - 10.3390/antiox10030497

M3 - SCORING: Journal article

C2 - 33806982

AN - SCOPUS:85102783704

VL - 10

JO - ANTIOXIDANTS-BASEL

JF - ANTIOXIDANTS-BASEL

SN - 2076-3921

IS - 3

M1 - 497

ER -