title: Angiotensin II induces the generation of procoagulant microparticles by human mononuclear cells via an angiotensin type 2 receptor-mediated pathway.
abstract: BACKGROUND
  Microparticles are small vesicles shed by cells upon activation and during apoptosis which participate in physiologically relevant phenomena, including blood coagulation. Intracellular calcium mobilization is one of the mechanisms of microparticle generation during cell activation. Because the renin-angiotensin system has been proposed as a link between hypertension and increased thrombotic risk, we investigated whether angiotensin II upregulates the generation of procoagulant microparticles by human mononuclear cells.
  
  
  METHODS
  Human mononuclear cells were exposed to angiotensin II for 15min. Intracellular calcium concentration was assessed by a Fluo 4 based kit. The supernatants were analyzed for both microparticle content, with a commercially available kit based on phosphatidylserine analysis, and microparticle-associated tissue factor, with a one-stage clotting assay.
  
  
  RESULTS
  Intracellular calcium concentration is increased upon exposure of mononuclear cells to angiotensin II. Incubation with angiotensin II stimulates microparticles release; microparticle-associated tissue factor is also upregulated. The effect is inhibited by an angiotensin receptor type 2 antagonist (PD123319) and not by two angiotensin type 1 antagonists (Losartan and Olmesartan).
  
  
  CONCLUSIONS
  Angiotensin receptor 2-mediated upregulation of tissue factor-bearing, procoagulant microparticle generation represents a novel mechanism linking the renin-angiotensin system to thrombosis.
authors: Laboratorio di Biologia Cellulare Respiratoria; Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università degli Studi di Pisa e Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors: Cinzia
authors: C
authors: Cordazzo
authors: Tommaso
authors: T
authors: Neri
authors: Silvia
authors: S
authors: Petrini
authors: Stefania
authors: S
authors: Lombardi
authors: Cristina
authors: C
authors: Balìa
authors: Silvana
authors: S
authors: Cianchetti
authors: Yuri
authors: Y
authors: Carmazzi
authors: Pierluigi
authors: P
authors: Paggiaro
authors: Roberto
authors: R
authors: Pedrinelli
authors: Alessandro
authors: A
authors: Celi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D013925:Thromboplastin