Perspective: Collagen induced platelet activation via the GPVI receptor as a primary target of colchicine in cardiovascular disease

Gabrielle J Pennings; Caroline J Reddel; Vivien M Chen; Sonali R Gnanenthiran; Leonard Kritharides

doi:10.3389/fcvm.2022.1104744

Perspective: Collagen induced platelet activation via the GPVI receptor as a primary target of colchicine in cardiovascular disease

Front Cardiovasc Med. 2023 Jan 19:9:1104744. doi: 10.3389/fcvm.2022.1104744. eCollection 2022.

Authors

Gabrielle J Pennings^{1

2}, Caroline J Reddel¹, Vivien M Chen^{3

4}, Sonali R Gnanenthiran^{1

2

5}, Leonard Kritharides^{1

2}

Affiliations

¹ Vascular Biology Group, ANZAC Research Institute, The University of Sydney, Concord, NSW, Australia.
² Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia.
³ Department of Haematology, Concord Repatriation General Hospital, Concord, NSW, Australia.
⁴ Platelet, Thrombosis Research Laboratory, ANZAC Research Institute, The University of Sydney, Concord, NSW, Australia.
⁵ The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.

Abstract

Colchicine has been demonstrated to reduce cardiovascular death, myocardial infarction (MI), ischemic stroke, and ischemia-driven coronary revascularization in people with coronary artery disease (CAD). These reductions were observed even in patients already taking antiplatelet therapy. As well as having anti-inflammatory effects, colchicine demonstrates antiplatelet effects. We propose that colchicine's antiplatelet effects primarily target collagen-induced platelet activation via the collagen receptor, glycoprotein (GP)VI, which is critical for arterial thrombosis formation. In settings such as stroke and MI, GPVI signaling is upregulated. We have demonstrated in vitro that therapeutic concentrations of colchicine lead to a decrease in collagen-induced platelet aggregation and alter GPVI signaling. Clinical studies of colchicine given for 6 months lead to a significant reduction in serum GPVI levels in CAD patients, which may ameliorate thrombotic risk. Future evaluation of the effects of colchicine in clinical trials should include assessment of its effects on collagen-mediated platelet activation, and consideration be given to quantifying the contribution of such antiplatelet effects additional to the known anti-inflammatory effects of colchicine.

Keywords: GPVI; cardiovascular disease (CVD); colchicine; platelet activation; stroke.