Platelet collagen receptors: A new target for inhibition?

Collagen is a major component of extracellular matrix and a wide variety of types exist. Cells recognise collagen in different ways depending on seque nce and structure. They can recognise predominantly primary sequence, they may require triple-helical structure or they can require fibrillar structur es. Since collagens are major constituents of the subendothelium that deter mine the thrombogenicity of the injured or pathological vessel wall, a majo r role is induction of platelet activation and aggregation as the start of repair processes. Platelets have at least two direct and one indirect (via von Willebrand factor) receptors for collagen, and collagen has specific re cognition motifs for these receptors. These receptors and recognition motif s are under intensive investigation in the search for possible methods to c ontrol platelet activation in vivo. A wide range of proteins has been ident ified and, in part, characterised from both haematophageous insects and inv ertebrates but also from snake venoms that inhibit platelet activation by c ollagen or induce platelet activation via collagen receptors on platelets. These will provide model systems to test the effect of inhibition of specif ic collagen-platelet receptor interactions for both effectiveness as well a s for side effects and should provide assay systems for the development of small molecule inhibitors. Since platelet inhibitors for longterm prophylax is of cardiovascular diseases are still in clinical trials there are many u nanswered questions about long-term effects both positive and negative. The major problem which still has to be definitively solved about these altern ative approaches to inhibition of platelet activation is whether they will show advantages in terms of dose-response curves while offering decreased r isks of bleeding problems. Preliminary studies would seem to suggest that t his is indeed the case.