Hemostasis and Thrombosis

Hemostasis is a complex phenomenon involving numerous coagulation factors. These factors circulate as inactive zymogens (inactive enzyme precursor) and act by cleaving downstream proteins so that they become active enzymes. The role of FVII in secondary hemostasis while forming a complex with TF is of primary importance. It was thought that the two pathways of coagulation cascade, the intrinsic (platelet) pathway and the extrinsic (FVII) pathway were equally important, but it is now known that the primary pathway for the initiation of blood coagulation is the TF-activated extrinsic pathway. FVII has a pivotal role in activating the common pathway of the clotting cascade and thrombin formation. The Mediterranean Diet, (MeD) Extra Virgin Olive Oil (EVOO), and polyphenols have been shown to affect several coagulation factors. The circulating level of FVII is deeply influenced by diet. There is a substantial increase in FVII circulating levels in the postprandial phase. The intake of dietary fat is the main determinant of the postprandial FVII plasma level. The ratio of Saturated Fatty Acids to Mono-Unsaturated Fatty Acids (MUFA) is crucial to postprandial levels of FVII. Diets rich in MUFA (i.e., olive oil, are associated with a significantly lower postprandial peak level of FVII and likely explain the lower rates of Coronary Heart Disease (CHD). in countries in which the diet is habitually rich in MUFAs, such as the Southern European countries. Gene polymorphisms in the FVII promoter region modulate FVII circulating levels. Some of these polymorphismsare associatedwithlower levels of circulating FVII. Also, platelet activity is influenced by diet. The n-3 Polyunsaturated Fatty Acids (PUFAs) Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) actively reduce platelet aggregation. This effect results from several mechanisms (i) competition with arachidonic acid, replacing active TxA2 with TxA3; (ii) inhibition of cyclooxygenase; and (iii) a direct antagonistic effect on the TxA2e prostaglandin H2 receptor in human platelets. Polyphenols of EVOO, particularly luteolin, also reduce platelet aggregability, acting as an inhibitor of platelet PDE3. Probably the most exciting data are those concerning the effects of the MeD in modulating gene expression. Dietary interventions have been demonstrated to modulate the expression of pro-atherothrombotic and inflammation genes actively even in high-risk populations. SFAs upregulate both proinflammatory and proatherothrombotic genes, whereas the MeD, EVOO, and polyphenols downregulate the expression of these genes. The MeD, which is rich in olive oil, MUFAs, and polyphenols were demonstrated to exert a modulatory effect toward a protective mode on genes related to chronic degenerative diseases, oxidation, inflammation, and thrombosis (modulating the activity of TF, TFP1, and thrombin). The phenolic compounds present in EVOO appear to be responsible for the transcriptomic effects, as demonstrated in randomized, controlled human studies in which similar olive oils, but with different phenolic contents, were tested.