title: Angiotensin II-dependent hypertension causes reversible changes in the platelet proteome.
abstract: OBJECTIVE
  Hypertension is a risk factor for arterial thrombosis. We investigated the effects of angiotensin II (ANG II)-dependent hypertension on the platelet proteome.
  
  
  RESULTS
  Hypertension was induced in cyp1a1ren-2 transgenic rats by feeding indole-3-carbinol (n = 10) and in Fischer 344 rats by subcutaneously infusing ANG II (n = 7). After 14 days of hypertension (SBP 180 mmHg) and 10 days after normalization of blood pressure, changes in the platelet proteome were assessed by two-dimensional differential in-gel electrophoresis. In a subset of animals (n = 4), repeated blood withdrawals were performed. Of 1040 protein spots, 45 displayed hypertension-associated changes (>1.5-fold, P < 0.01) in both models (34 increased, 11 decreased). All were reversible within 10 days. Thirty-eight spots were identified by mass spectrometry and assigned to 20 distinct proteins. The majority of spots with increased intensity constituted protein fragments. Repeated blood withdrawals and stimulation of megakaryocytopoiesis by a thrombopoietin receptor agonist induced changes in the same protein spots but in the opposite direction to those induced by ANG II-dependent hypertension.
  
  
  CONCLUSIONS
  ANG II-dependent hypertension is associated with enhanced protein degradation in platelets. As these changes are reversible, the proteins identified might be used to develop a biomarker for monitoring recent blood pressure history.
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Gebhard
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.forename: Barbara
authors.initials: B
authors.lastname: Peters
authors.forename: Manuela
authors.initials: M
authors.lastname: Gesell-Salazar
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.forename: Beate
authors.initials: B
authors.lastname: Kuttler
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Clemetson
authors.forename: Christian
authors.initials: C
authors.lastname: Scharf
authors.forename: Jörg
authors.initials: J
authors.lastname: Peters
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Rainer
authors.initials: R
authors.lastname: Rettig
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D012083:Renin / Q000378:metabolism; D012307:Risk Factors
chemical_list: D007211:Indoles; D020543:Proteome; D000804:Angiotensin II; D000450:Aldosterone; C016517:indole-3-carbinol; D012083:Renin