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Tesi etd-05282015-132551


Thesis type
Tesi di specializzazione (5 anni)
Author
BALIA, CRISTINA
URN
etd-05282015-132551
Title
Renin Angiotensin System-mediated modulation of inflammation-induced Tissue Factor expression
Struttura
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
PATOLOGIA CLINICA
Commissione
relatore Prof. Pedrinelli, Roberto
Parole chiave
  • tissue factor
  • coagulation
  • inflammation
  • Renin Angiotensin system blockers
  • high glucose
  • Renin Angiotensin system
Data inizio appello
22/06/2015;
Consultabilità
completa
Riassunto analitico
Background: An intricate cross-talk connects Tissue Factor (TF) to inflammation and is amplified by locally active angiotensin(ang)II, that stimulates TF expression. High glucose may activate pro-inflammatory pathways and increase glucose-mediated angII production.<br>Aim: To evaluate the effect of Renin Angiotensin System (RAS) blockade on TF expression in peripheral blood mononuclear cells (PBMCs) exposed to normal glucose (NG) and high glucose (HG), and stimulated by lipopolysaccharide (LPS), a well known pro-inflammatory agent. <br>Methods: PBMCs, from healthy donors were LPS-stimulated and exposed to NG and HG. TF mRNA levels, antigen expression and pro-coagulant activity were assessed by Real Time-PCR, ELISA and 1-stage clotting assay respectively, in absence or presence of pharmacological intervention.<br>Results: LPS stimulation increased TF expression in NG, an effect down-regulated by Aliskiren, a direct renin inhibitor, zofenopril, an angiotensin converting enzyme inhibitor, olmesartan, an angII type1 receptor (AT1R) blocker and Compound21, an highly selective angII type 2 receptor (AT2R) agonist. As compared with NG, HG amplified the LPS-stimulation of TF expression, an effect that Aliskiren, Zofenopril and Compound21 down- regulated in HG with a similar behavior to that in NG, while OLM activity was potentiated in HG. <br>Conclusions: Our data disclose tight connections between the apparently unrelated domains of innate immunity and metabolic and cardiovascular regulation, expanding the restrictive view of angII as a peptide mainly involved in the control of blood pressure and water and salt homeostasis.<br>
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