ETD

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Tesi etd-03152012-172735


Tipo di tesi
Tesi di dottorato di ricerca
Autore
CORDAZZO, CINZIA
URN
etd-03152012-172735
Titolo
Studies on the mechanisms of generation of microparticles and their role in the pathophysiology of coagulation
Settore scientifico disciplinare
MED/18
Corso di studi
CHIRURGIA, BIOTECNOLOGIE E IMMUNOLOGIA DEI TRAPIANTI
Relatori
tutor Celi, Alessandro
commissario Paolicchi, Aldo
commissario Colantuoni, Antonio
commissario Cremisi, Federico
tutor Prof.ssa Longoni, Bianca Maria
Parole chiave
  • thrombotic events
  • TNF-alpha
  • sigarette smoke
  • pancreatic islet tranplantation
  • LPS
  • microparticles
  • IBMIR
  • hypertension
  • angiotensin II
  • vascular diseases
Data inizio appello
28/03/2012
Consultabilità
Completa
Riassunto
Microparticles are phospholipid vesicles shed by cells upon activation or during apoptosis. MP range in size from 50 nm to 1 µm [1]. Recent evidence have demonstrated that MP are involved in numerous physiological processes, including inflammation and blood coagulation. Because of the presence of negatively charged phospholipids on the outer leaflet of MP, these structures have been long attributed a role in blood coagulation, a process that requires the assembly of multimolecular complexes on the surface of negatively charged phospholipid membranes. More recently, however, it has become evident that MP also carry other components of the parental cell besides the phospholipids, which greatly broaden the spectrum of their potential effects as intercellular mediators [1]. For example, the presence on monocyte-derived MP of tissue factor, an essential cofactor for the initiation of blood coagulation [2], adds to their role in blood coagulation and thrombus formation [3].
The role of leukocyte- and endothelial cell-derived MP in coagulation processes involved both in physiological blood homeostasis both in vascular diseases has also been extensively investigated. MP can modulate cytokine expression in monocytes and endothelium; promote leukocyte-leukocyte aggregation and recruitment through P-selectin. Elevated platelet-derived MP associated with calpain activity have been documented in plasma of patients with thrombotic thrombocytopenic purpura [4]. Endothelial MP express the von Willebrand factor multimers that promote platelet aggregation and increase their stability, promoting the stability of the thrombus.
Here we investigated the role of MP in thrombotic reaction associated to two widely widespread factors of risk to develop vascular diseases, like cigarette smoke and hypertension. In addition, we analyzed the role of MP bearing TF as mediators in the Instant blood-mediated inflammatory reaction, main responsible for the negative outcome of the pancreatic islets transplantation in type 1 diabetes.
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