[Thrombogenicity of the vessel: role of microfibrils and of collagen]

Thrombogenicity of the vessel wall: role of the microfibrils and collagen. The study of platelet adhesion to rabbit aortic subendothelium preincubated with highly specific collagenase has revealed that platelets adhere to the microfibrils of the elastic lamina. To certify that an interaction between microfibrils and platelets can occur, microfibrils from two different origins were isolated: placental microfibrils extracted from the villi of human placenta, and aortic microfibrils extracted from adult bovine aorta. Both preparations were histologically homogeneous, and differed in their amino acid composition with an acidic character more pronounced for placental than for aortic microfibrils. Both preparations were able to induce platelet aggregation in plasma, but not after platelet isolation and resuspension in buffer. An interesting feature was the fact that when normal platelets were isolated, washed and resuspended in plasma from severe VWD patients, they were not aggregated by placental or aortic microfibrils. This defect was corrected after perfusion of cryoprecipitate to one patient. Moreover, monoclonal antibody directed against platelet glycoprotein Ib inhibited the aggregation of platelets to microfibrils, not to collagen; this suggested that an axis platelet GPI-FVIII/VWF-microfibrils could represent a pathway for platelet/subendothelium interaction. The adhesion of platelets to collagen seems to involve the staggering of a short amino acid sequence along a collagen fibre. This possibility arises from the requirement for the preservation of the quaternary structure of collagen in the induction of platelet adhesion/aggregation in vitro, and also from the identification and synthesis of a nonapeptide derived from type III collagen, which is also to specifically inhibit the aggregation of platelets by collagen, following its binding to platelet membrane.