Chapter 6: Conclusions
Although originally thought to represent cell debris devoid of physiological meaning, MP are now known to participate in different physiological phenomena. MP-mediated upregulation of the synthesis of proinflammatory agonists by endothelial cells and fibroblasts, for example, is becoming a well recognized determinant of inflammation [27]. MP have a high procoagulant potential and play an important role in promoting prothrombotic events.
As part of an attempt to further elucidate the mechanisms underlying MP-induced prothrombotic phenotype, the aim of the present work was to investigate whether two well known risk factors for vascular diseases, namely CSE and hypertension, can induce the generation of procoagulant MP. Our data demonstrated that mononuclear cells exposed to CSE can generate MP-TF+ through a mechanism dependent on a rapid-intracellular calcium mobilization. Stimulation with Ang II, the main effector of RAS, induces mononuclear cells to generate MP-TF+ both via a specific AT2-mediated pathway and via a rapid intracellular calcium increase. CSE and hypertension are well known risk factors for atherosclerosis and both can induce generation of MP-TF+, able to enhance the procoagulant and proinflammatory process that leads to the formation of the atheroma plaque. As previous studies have already shown, our data confirm that the modulation of the intracellular calcium mobilization seems to be required in the generation of MP [5]. Thrombotic events and atherosclerosis have been demonstrated to be among the most common complications of diabetes. Transplantation of pancreatic islets is the most promising clinical practice for type 1 diabetes, leading to insulin independence. IBMIR represents one of the causes to induce the loss of pancreatic transplanted islets. Our data show that rat pancreatic islets upon stimulation with proinflammatory agents can release MP-TF+, suggesting them as possible mediators of prothrombotic reactions.
In conclusion, evaluating three different conditions characterized by a high prothrombotic potential our data show the generation of MP characterized by high procoagulant activity due to both exposure of PS both the presence of TF, through the activation of a rapid-intracellular calcium mobilization mechanism. These evidences contribute to establish the crucial role of MP as mediators of thrombotic events. Further investigations on their membrane composition and the intracellular mechanisms involved in their generation can open the way to develop new drugs direct to block MP, promoting the prevention and the treatment of cardiovascular diseases.
