PARTICIPATION OF THROMBOTIC AND HEMOSTATIC MECHANISMS IN THE INITIAL-STAGES OF ATHEROSCLEROSIS

The factors of thrombosis (endothelium, haemostasis, coagulation, fibr inolysis) are implicated from the initiating phase of atherosclerotic lesions. Their participation is more established land studied) in the later phases of intraluminal evolution of atherosclerosis, of thromboe mbolic complications of the lesions and interventional procedures. The traditional theory of response to physical lesions of the endothelium as an initiating factor of atherosclerotic lesions, which gave platel ets an essential role, has been replaced by that linking an early func tional lesion of the endothelium and a cellular response by monocytes infiltrating the vessel wall, becoming macrophages. The macrophages pa rticipate in changes of the LDL in the wall, ingest the lipids at the same time as the smooth muscle cells which have migrated and prolifera ted from the media to the intima. The lipid overload, especially with oxidised LDL, is intracellular at first in these foam cells, then extr acellular as the cells die. During the early stages, all the tissue fa ctors of activation and development of coagulation are present in the vessel wall and then within the lesion. This intra-cellular coagulatio n results in the production of thrombi in the tissues and the transfor mation of fibrinogen to fibrin. These stages precede and participate i n cellular proliferation and extracellular lipid deposits. Factors of tissular thrombolysis (the uPA pathway) play a part in cellular immigr ation and proliferation. It is only at a later stage that the lesion a ctivates intravascular coagulation and fibrinolysis which, in conditio ns of variable equilibrium, will result in the clinical complications of the atherosclerotic process. All these factors therefore participat e firstly in the tissues and then within the lumen, in the progression and complications of atherosclerosis which for these reasons is often called atherothrombotic disease. The comprehension of these mechanism s is essential for the development and interpretation of tests and tre atment applied to different stages of the disease, which is all the mo re complex given that in a given patient at a given time, lesions at d ifferent stages are present in the arterial network.