RELATIONS ENTRE LES ACTIVATEURS DU PLASMINOGENE ET LES CAPACITES REGENERATIVES DU MUSCLE SQUELETTIQUE DU RAT

International audienc

Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques

BACKGROUND: Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis. AIM: To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo. METHODS AND RESULTS: Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed. CONCLUSIONS: These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.status: publishe

Augmented renal clearance. An unnoticed relevant event

Altres ajuts: Blood Purification Therapies Collaboration Group; Catalan Society of Intensive Care Medicine.Augmented renal clearance (ARC) is a phenomenon that can lead to a therapeutic failure of those drugs of renal clearance. The purpose of the study was to ascertain the prevalence of ARC in the critically ill patient, to study the glomerular filtration rate (GFR) throughout the follow-up and analyze the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimation formula and measured GFR. Observational, prospective, multicenter study. ARC was defined as a creatinine clearance greater than 130 ml/min/1.73 m. Eighteen hospitals were recruited. GFR measurements carried out twice weekly during a 2-month follow-up period. A total of 561 patients were included. ARC was found to have a non-negligible prevalence of 30%. More even, up to 10.7% already had ARC at intensive care unit (ICU) admission. No specific pattern of GFR was found during the follow-up. Patients in the ARC group were younger 56.5 (53.5-58.5) versus 66 (63.5-68.5) years than in the non-ARC group, p < 0.001. ICU mortality was lower in the ARC group, 6.9% versus 14.5%, p = 0.003. There was no concordance between the estimation of GFR by the CKD-EPI formula and GFR calculated from the 4-h urine. ARC is found in up to 30% of ICU patients, so renal removal drugs could be under dosed by up to 30%. And ARC is already detected on admission in 10%. It is a dynamic phenomenon without an established pattern that usually occurs in younger patients that can last for several weeks. And the CKD-EPI formula does not work to estimate the real creatinine clearance of these patients