5 research outputs found
Metodologie per la sostituzione dei dati mancanti: applicazione delle procedure basate sulla simulazione ai dati dello studio MAIDS
Quali aspetti dell'esperienza del motociclista proteggono dal rischio d'incidente? Un'analisi non parametrica
Statistiche correnti nazionali sugli incidenti stradali di motocicli e ciclomotori e indagini ad hoc: l’esperienza dello studio MAIDS
Long Pentraxin 3/TSG-6 Interaction: A Biological Rheostat for Fibroblast Growth Factor 2–Mediated Angiogenesis
Objective—Angiogenesis is regulated by the balance between pro- and antiangiogenic factors and by extracellular matrix
protein interactions. Fibroblast growth factor 2 (FGF2) is a major proangiogenic inducer inhibited by the interaction with
the soluble pattern recognition receptor long pentraxin 3 (PTX3). PTX3 is locally coexpressed with its ligand tumor
necrosis factor-stimulated gene-6 (TSG-6), a secreted glycoprotein that cooperates with PTX3 in extracellular matrix
assembly. Here, we characterized the effect of TSG-6 on PTX3/FGF2 interaction and FGF2-mediated angiogenesis.
Methods and Results—Solid phase binding and surface plasmon resonance assays show that TSG-6 and FGF2 bind the
PTX3 N-terminal domain with similar affinity. Accordingly, TSG-6 prevents FGF2/PTX3 interaction and suppresses the
inhibition exerted by PTX3 on heparan sulfate proteoglycan/FGF2/FGF receptor complex formation and on
FGF2-dependent angiogenesis in vitro and in vivo. Also, endogenous PTX3 exerts an inhibitory effect on vascularization
induced by FGF2 in a murine subcutaneous Matrigel plug assay, the inhibition being abolished in Ptx3-null mice
or by TSG-6 treatment in wild-type animals.
Conclusion—TSG-6 reverts the inhibitory effects exerted by PTX3 on FGF2-mediated angiogenesis through competition
of FGF2/PTX3 interaction. This may provide a novel mechanism to control angiogenesis in those pathological settings
characterized by the coexpression of TSG-6 and PTX3, in which the relative levels of these proteins may fine-tune the
angiogenic activity of FGF2
Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial
Background: The long pentraxin PTX3 is a key component of the humoral arm of innate immunity related to sepsis severity and mortality. We evaluated the clinical and prognostic significance of circulating PTX3 in the largest cohort ever reported of patients with severe sepsis or septic shock. Materials and methods: Plasma PTX3 was measured on days 1, 2 and 7 after randomization of 958 patients to albumin or crystalloids for fluid resuscitation in the multicentre Albumin Italian Outcome Sepsis (ALBIOS) trial. We tested the association of PTX3 and its changes over time with clinical severity, prevalent and incident organ dysfunctions, 90-day mortality and treatment. Results: PTX3 was high at baseline (72 [33\u2013186] ng/mL) and rose with the severity and number of organ dysfunctions (P < 0\ub7001) and the incidence of subsequent new failures. The PTX3 concentration dropped from day 1 to 7, but this decrease was less pronounced in patients with septic shock (P = 0\ub70004). Higher concentrations of PTX3 on day 1 predicted incident organ dysfunctions. Albumin supplementation was associated with lower levels of PTX3 in patients with septic shock (P = 0\ub7005) but not in those without shock. In a fully adjusted multivariable model, PTX3 on day 7 predicted 90-day mortality. Smaller drops in PTX3 predicted higher 90-day mortality. Conclusions: In severe sepsis and septic shock, early high PTX3 predict subsequent new organ failures, while a smaller drop in circulating PTX3 over time predicts an increased risk of death. Patients with septic shock show lower levels of PTX3 when assigned to albumin than to crystalloids