Circulating Microparticles from Septic Shock Patients Exert Protective Role on Vascular Function. Export

@article{citeulike:3181860, abstract = {RATIONALE: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles. OBJECTIVES: We characterised circulating microparticles from both non-septic and septic shock subjects and evaluated their contribution on vascular function. METHODS: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 non-septic subjects by flow cytometer. Then, microparticles were injected i.v to mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide and cyclooxygenase metabolites production were analyzed. RESULTS: Circulating levels of microparticles, platelet- and endothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced but not reduced sensitivity of contraction of mouse aortas in response to serotonin. Interestingly, septic microparticles enhanced contraction of aortas from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor Rho-kinase inhibitor-sensitive mechanisms. Besides, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O2(-) overproduction. The non-selective cyclooxygenase-2 inhibitor, indomethacin, and the specific thromboxane A2 antagonist, SQ-29548, either reduced or abolished contraction in aorta from mice treated with non-septic and septic microparticles, respectively. The effect of septic microparticles was associated with an increased thromboxane A2 production, and was sensitive to a selective thromboxane A2 antagonist. CONCLUSION: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock.}, address = {INSERM, U771, Universite d'Angers, Angers, France.}, author = {Mostefai, Hadj Ahmed A. and Meziani, Ferhat and Mastronardi, Maria Letizia L. and Agouni, Abdelali and Heymes, Christophe and Sargentini, Cyrille and Asfar, Pierre and Martinez, Maria Carmen C. and Andriantsitohaina, Ramaroson}, citeulike-article-id = {3181860}, citeulike-linkout-0 = {http://dx.doi.org/10.1164/rccm.200712-1835OC}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18723433}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18723433}, day = {21}, doi = {10.1164/rccm.200712-1835OC}, issn = {1535-4970}, journal = {American journal of respiratory and critical care medicine}, keywords = {microparticles, nitricoxide}, month = {August}, posted-at = {2008-09-02 13:35:31}, priority = {2}, title = {Circulating Microparticles from Septic Shock Patients Exert Protective Role on Vascular Function.}, url = {http://dx.doi.org/10.1164/rccm.200712-1835OC}, year = {2008} }

TY - JOUR ID - citeulike:3181860 L3 - citeulike-article-id:3181860 N2 - RATIONALE: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles. OBJECTIVES: We characterised circulating microparticles from both non-septic and septic shock subjects and evaluated their contribution on vascular function. METHODS: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 non-septic subjects by flow cytometer. Then, microparticles were injected i.v to mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide and cyclooxygenase metabolites production were analyzed. RESULTS: Circulating levels of microparticles, platelet- and endothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced but not reduced sensitivity of contraction of mouse aortas in response to serotonin. Interestingly, septic microparticles enhanced contraction of aortas from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor Rho-kinase inhibitor-sensitive mechanisms. Besides, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O2(-) overproduction. The non-selective cyclooxygenase-2 inhibitor, indomethacin, and the specific thromboxane A2 antagonist, SQ-29548, either reduced or abolished contraction in aorta from mice treated with non-septic and septic microparticles, respectively. The effect of septic microparticles was associated with an increased thromboxane A2 production, and was sensitive to a selective thromboxane A2 antagonist. CONCLUSION: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock. JF - American journal of respiratory and critical care medicine SN - 1535-4970 AD - INSERM, U771, Universite d'Angers, Angers, France. TI - Circulating Microparticles from Septic Shock Patients Exert Protective Role on Vascular Function. KW - microparticles KW - nitricoxide AU - Mostefai, Hadj Ahmed AU - Meziani, Ferhat AU - Mastronardi, Maria Letizia AU - Agouni, Abdelali AU - Heymes, Christophe AU - Sargentini, Cyrille AU - Asfar, Pierre AU - Martinez, Maria Carmen AU - Andriantsitohaina, Ramaroson PY - 2008/08/21/ UR - http://dx.doi.org/10.1164/rccm.200712-1835OC ER -