Platelet collagen receptors (Glycoprotein VI and Integrin alpha-2 beta-1) (GPVI/α2β1)

Glycoprotein VI (GPVI) and Integrin alpha-2 beta-1 (α2β1) are the two primary receptors on the platelet surface that mediate interaction with subendothelial collagen exposed during vascular injury [1, 2]. GPVI is a member of the immunoglobulin superfamily and serves as the primary signaling receptor; its binding to collagen triggers a robust activation cascade via the Fc receptor gamma-chain, leading to platelet shape change and aggregation [1]. Integrin α2β1, also known as VLA-2, primarily facilitates the stable, high-affinity adhesion of platelets to the collagen matrix, which is essential for thrombus stabilization under the high shear stress conditions of arterial blood flow [2]. This dual-receptor system is a critical driver of arterial thrombosis, making it a high-priority target for next-generation antithrombotic therapies [3]. Unlike traditional antiplatelet agents such as aspirin or P2Y12 inhibitors, targeting the GPVI/α2β1-collagen axis is hypothesized to prevent pathological thrombus formation with a significantly reduced risk of bleeding complications, as these receptors are largely redundant for primary hemostasis [3, 4]. Clinical candidates like glenzocimab and revacept are currently being evaluated for their efficacy in treating acute ischemic stroke and other cardiovascular conditions [3, 4]. Citations: [1] Nieswandt B, Watson SP. Blood. 2003;102(2):449-461. [2] He L, et al. Trends Cardiovasc Med. 2003;13(2):67-71. [3] Lebozec K, et al. Expert Opin Biol Ther. 2021;21(7):841-848. [4] Ungerer M, et al. J Am Coll Cardiol. 2020;76(23):2748-2757.

Other names

GP6VLA-2CD49b/CD29Platelet glycoprotein VIIntegrin alpha-2 beta-1Collagen receptor complex

Inhibition of platelet-collagen interaction by blocking receptor binding sites or sequestering collagen fibers, thereby preventing platelet activation and stable adhesion.