VPB0778 - Platelet proteomics reveals an inflammatory phenotype of platelets in type 2 diabetes

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Yvonne X. Kong, MBBS MSc

PhD Candidate
Haematology Research Group, Charles Perkins Centre, University of Sydney
Camperdown, New South Wales, Australia

Co-Author(s)

RR

Rajan Rehan

Cardiologist
Cardiology Dept, Royal Prince Alfred Hospital
Sydney, New South Wales, Australia
JW

James Weaver

Cardiologist
Department of Cardiology, Royal Prince Alfred Hospital
Sydney, New South Wales, Australia
CH

Callum Houlahan

Research Assistant
Haematology Research Group, The Heart Research Institute, University of Sydney; Faculty of Medicine & Health, Central Clinical School, University of Sydney
Sydney, New South Wales, Australia
BJ

Bede Johnston

Research Assistant
Haematology Research Group, The Heart Research Institute, University of Sydney; Faculty of Medicine & Health, Central Clinical School, University of Sydney
Sydney, New South Wales, Australia
KP

Kang-Yu Peng

Research Officer
Haematology Research Group, The Heart Research Institute, University of Sydney; Faculty of Medicine & Health, Central Clinical School, University of Sydney
Sydney, New South Wales, Australia
MC

Michelle Cielesh

Research Assistant
Larance Laboratory, Charles Perkins Centre, University of Sydney
Sydney, New South Wales, Australia
ML

Mark Larance

Group Leader
Larance Laboratory, Charles Perkins Centre, University of Sydney
Sydney, New South Wales, Australia
FP

Freda Passam

Group Leader
Haematology Research Group, Charles Perkins Centre, University of Sydney
Sydney, New South Wales, Australia

Background: Platelets in patients with type 2 diabetes are “hyperactive” resulting in decreased efficacy of antiplatelet agents in the prevention of cardiovascular events [1]. Platelet proteomics allows quantitative analysis of mediators of platelet hyper-reactivity. However, a dedicated study of the platelet proteome in patients with diabetes and cardiovascular disease (CVD) has not been performed previously.

Aims: To identify proteomic differences in the platelets of patients with or without diabetes with, or at risk of, coronary artery disease and to correlate proteomic changes with functional platelet assays.

Methods: Forty-two patients with type 2 diabetes and 34 patients non-diabetic patients, matched by sex and age, were recruited through the Coronary catheterization lab of Royal Prince Alfred Hospital, Sydney (Ethics X20-0085) [2]. Platelets were isolated from whole blood and separated into platelet lysate and releasate fractions (with or without pre-activation with low dose thrombin 0.025 U/ml). Platelet function was assessed by platelet aggregation and by the mobilization of P selectin and PAC-1 after stimulation with a panel of agonists. Releasate and lysate proteins were identified by LC-MS/MS using a Thermo Lumos Tribrid Orbitrap instrument [3].

Results: Platelets from patients with or without diabetes had similar surface P-selectin and PAC-1 expression by flow cytometry. Platelets from patients with diabetes showed increased aggregation to 5 uM ADP and 1 uM U44619. There was a decrease in cardioprotective proteins, e.g. superoxidase dismutase 2 and myeloid derived growth factors released by platelets from patients with diabetes after thrombin stimulation. Secreted chemokines, e.g. CXCL3 and CXCL5, were significantly increased in the releasate in patients with diabetes, and was also increased in male compared to female patients regardless of diabetic status.

Conclusion(s): These studies identify platelets as mediators of the inflammatory status in type 2 diabetes. Platelet proteomics is a promising tool for the identification of platelet biomarkers in CVD.