The platelet-vessel wall interaction in experimental atherosclerosis and ischaemic heart disease with special reference to thrombopoiesis.
Platelets and their interaction with the vessel wall play a role in atherogenesis and in the formation of the coronary thrombus. Supplementation of the diet with n-3 PUFA shifts the platelet-vessel wall interaction in anti-thrombotic direction in healthy persons and in patients with IHD. This is in part caused by an inhibition of Tx synthesis and also by an increased synthesis of PGI2 and PGI3 in the vessel wall. However, the clinical significance of these findings needs to be elucidated in clinical trials. Large, dense platelets are more reactive than small ones. Platelet size and density are determined at thrombopoiesis. Large, reactive platelets have in states with an increased platelet demand been shown to be produced from large, high-ploidy megakaryocytes. In patients with thrombopoiesis in steady-state an inverse relation between the bleeding time and both the DNA content and the size of the bone marrow megakaryocytes has been demonstrated. The bone marrow megakaryocytes in these patients were larger in men than in women, which may explain the sex difference in bleeding time observed by others. In experimental atherosclerosis changes in megakaryocyte size have been demonstrated. The significance of these changes are still unclear. In a single study stimulation of the platelet-megakaryocyte axis was associated with an acceleration of experimental atherosclerosis. This study suggests that large, high ploidy megakaryocytes may produce a large amount of atherogenic platelets that may be responsible for the increased formation of atheroma in this model. However, due to the complexity of the study design this hypothesis needs verification in other experimental and clinical studies. In patients suffering from an AMI the mean platelet volume is increased. The bleeding time is shortened at the time of infarction in these patients probably due to increased synthesis of TxA2, but an increased production of adrenaline may also be of importance. These large, reactive platelets present in AMI may be a reflection of an altered thrombopoiesis in these patients. It remains to be established whether these changes in platelet reactivity are present before the time of coronary thrombus formation.
Kristensen
S D
SD
Department of Clinical Chemistry, Aalborg Hospital, London, U.K.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001792:Blood Platelets / Q000502:physiology*; D003327:Coronary Disease / Q000209:etiology*; D003328:Coronary Thrombosis / Q000209:etiology; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D008533:Megakaryocytes / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D013928:Thromboxane A2 / Q000502:physiology
D005231:Fatty Acids, Unsaturated; D013928:Thromboxane A2; D011464:Epoprostenol