Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases.
Both inflammation and thrombosis can be orchestrated by the interactions between circulating cells, such as leukocytes and platelets, with vascular, endothelial and smooth muscle cells, which, during activation or apoptosis, can release circulating microparticles (MPs). Indeed, MPs are membrane vesicles with procoagulant and proinflammatory properties. MPs are present in blood from healthy individuals and in patients under several pathological states, for instance sepsis, preeclampsia, Crohn's disease and diabetes, strengthening the notion that MPs may play a role in these diseases. Circulating MPs or those generated in vitro from apoptotic T cells display deleterious effects on endothelial and/or vasomotor function. In contrast, MPs might be protective to endothelial cells. We have shown that MPs harboring the morphogen sonic hedgehog may represent a new therapeutic approach against endothelial dysfunction during acute severe endothelial injury. Indeed, these types of MPs induce NO release, decrease production of reactive oxygen species and induce angiogenesis from endothelial cells. This protective role for the endothelium was confirmed also by their in vivo injection in mice in which they were also able to reverse endothelial dysfunction in a model of heart ischemia/reperfusion. On the contrary, MPs from preeclamptic women compared to those from normal pregnant women showed pro-inflammatory properties in the vascular wall inducing vascular hyporeactivity in vessels from humans and mice. These effects were associated with complex interactions between NO and cyclooxygenase systems via endothelial cell activation. Altogether, these findings suggest that MPs can be considered as vectors of biological messages for vascular homeostasis, during immunity and inflammation. (+info)
The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation.
Measurement of platelet-derived microparticle levels in the chronic phase of cerebral infarction using an enzyme-linked immunosorbent assay.
Assessment of platelet function is a critical component of the treatment and secondary prevention of cerebral infarction, and measurement of platelet-derived microparticle (PDMP) levels using flow cytometry may be a good indicator of platelet function. However, the flow cytometric analysis is not feasible in a variety of clinical situations. The goal of the present study was to measure PDMP levels using an enzyme-linked immunosorbent assay (ELISA) in chronic cerebral infarction patients and to determine the utility of PDMP level measurement for the monitoring of the effect of cilostazol and aspirin. A crossover study was performed using 4-weeks of aspirin (100 mg/day) and 4-weeks of cilostazol (200 mg/day) in 18 patients. PDMP levels were also measured in 20 volunteers as controls. Experiments demonstrated that PDMP levels were significantly higher in chronic cerebral infarction patients (median 8.8 U/ml, interquartile range 5.1-14.9 U/ml, n=18) than in controls (median 5.5 U/ml, interquartile range 5.0-8.2 U/ml, n=20) (P=0.047). PDMP levels did not decrease after therapy with either aspirin (median 10.9 U/ml, interquartile range 6.2-17.9 U/ml, n=12) or cilostazol (median 9.2 U/ml, interquartile range 6.1-14.3 U/ml, n=12) compared with baseline PDMP levels in the 12 patients who completed this trial (median 11.4 U/ml, interquartile range 5.2-23.7 U/ml, n=12). There were no significant differences in PDMP levels between aspirin and cilostazol (P=0.61). In conclusion, PDMP levels as measured by ELISA were increased in patients with chronic cerebral infarction regardless of the anti-platelet therapy. This methodology may be a useful strategy of assessing platelet function in chronic cerebral infarction patients. (+info)
Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles.
Dynamics of circulating microparticles in liver transplant patients.
BACKGROUND & AIMS: Microparticles are small membrane vesicles released from the cell plasma membrane, particularly in cell stress, apoptosis and altered cellular viability. Hepatocellular carcinoma (HCC) is a hypervascular neoplasm with high levels of apoptosis and necrosis. We investigated the levels of circulating microparticles of both tumor and endothelial origins in liver transplant patients with hepatitis C (HepC) cirrhosis with and without HCC and compared them with healthy people and patients with partial hepatectomy. METHODS: Using immunolabeling of microparticles of different origin and flow cytometry-based enumeration of microparticles, the levels of circulating microparticles were studied in 8 patients with HepC and 8 patients with both HepC and HCC before and within two weeks after the transplant. RESULTS: The initial levels of circulating microparticles were increased in patients with HepC and HCC as compared to patients with HepC alone. They were also increased in liver transplant patients as compared to patients with partial hepatectomy or healthy people. Levels of circulating microparticles were dynamically changing after the transplant, showing an initial increase with a subsequent decrease by the end of the second week after surgery. In some patients with a complicated clinical outcome, the levels of microparticles were continuously increasing after the surgery. CONCLUSION: The levels of circulating microparticles of endothelial and hepatic origin in liver transplant patients dynamically change after surgery and correlate with the clinical outcome. Perspectively, the levels of circulating microparticles may be used in clinical practice as a marker of the functional status of the transplanted liver. (+info)
Diagnostic role of endothelial microparticles in vasculitis.