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

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.

African Swine Fever Virus I267L Is a Hemorrhage-Related Gene Based on Transcriptome Analysis

“…Apart from the coagulation cascades, the clotting process is always related to collagen-induced platelet activation [ 53 ]. Type I collagen is among the most abundant proteins in humans [ 54 ]; it is composed of two chains of collagen type I alpha 1 (COL1A1) and one chain of collagen type I alpha 2 (COL1A2) [ 55 ].…”

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives

“…Another thrombo-inflammatory indicator of injury is collagen, the signaling of which is also a promising drug target. When released from damaged cells (i.e., endothelial cells) collagen can directly induce platelet activation and aggregation through integrin α2β1 (glycoprotein GPIa-IIa) and glycoprotein VI (GPVI), but also indirectly through glycoprotein Ib-V-IX transmembrane protein complex found on the surface of platelets, which binds to the A1 domain of vWF that is immobilized on collagen upon vascular injury, mediating the attraction and binding of activated platelets to the injured site [31,[37][38][39][40][41]. There, the binding of collagen to GPVI induces a conformational change in the platelets shape, rapid calcium influx through the generation of inositol-1,4,5-triphosphate (IP 3 ) from the activation of phospholipase Cγ2 (PLCγ2)and phosphoinositide-3 kinase (PI3K), and the production and release of other secondary platelet agonists (i.e., thromboxanes among others) from the platelet granules (degranulation).…”