Angiotensin II-dependent hypertension causes reversible changes in the platelet proteome

Objective Hypertension is a risk factor for arterial thrombosis. We investigated the effects of angiotensin II (ANG II)-dependent hypertension on the platelet proteome. Methods and 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 180mmHg) 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. Conclusion 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. J Hypertens 29: 2126-2137 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.