RESEARCH ARTICLE Modifications by Olmesartan medoxomil treatment of the platelet protein profile of moderate hypertensive patients Daniel Sacristán 1 , María Marques 2 , José J Zamorano-León 1 , Manuel Luque 3 * , Juan Armengol 4 , Juan del Castillo 4 , Javier Martín 4 , Eva Delpón 5 , Priscila Ramos-Mozo 1 , Teresa P de Prada 1 , Juan Tamargo 5 , Alberto Barrientos 2 , Carlos Macaya 1 and Antonio López-Farré 1 1 Cardiovascular Research Unit of the Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain. 2 Nephrology Department, Universidad Complutense de Madrid, Spain. 3 Hypertension Unit, Hospital Clínico San Carlos, Madrid, Spain. 4 Emergency Unit. Hospital Clínico San Carlos, Universidad Complutense de Madrid, Spain. 5 Pharmacology Department. Medicine School, Universidad Complutense de Madrid, Spain. Olmesartan medoxomil is a new angiotensin II receptor blockers (ARB) which exhibits pleio- tropic effects that are not fully understood. Our aims were: i) to determine the effect of Olme- sartan medoxomil on blood pressure, lipid profile and renal functionality in moderately hyper- tensive patients with non-controlled blood pressure, ii) to determine if Olmesartan medoxomil may exert anti-inflammatory effects and modify the expression profile of platelet proteins. Thir- teen moderate hypertensive patients with non-controlled systolic blood pressure (SBP) and renal function classified as Kidney Disease Outcome Quality Initiative stage 2–3 were included. Patients were treated with Olmesartan medoxomil (20 mg/day) for 6 months. SBP, proteinuria and the plasma levels of cholesterol and low density lipoprotein (LDL)-cholesterol were reduced after the treatment. Olmesartan medoxomil did not modify the circulating plasma levels of a number of proteins associated with inflammation, but reduced the expression level of different platelet proteins including tropomyosin-b chain isotypes 3 and 4, serotransferrin isotypes 1 to 5, the leukocyte elastase inhibitor and the chloride intracellular channel-protein isotype 1. The expression of the gelsolin precursor isotype 4 was increased in the platelets after the treatment. In summary, Olmesartan medoxomil reduced SBP, total and LDL-cholesterol plasma levels and urinary protein excretion and induced changes in the expression of platelet proteins which may be related to some action of the drug at the megakaryocyte level. Received: July 24, 2007 Revised: March 27, 2008 Accepted: April 14, 2008 Keywords: Angiotensin II receptor blockers / Hypertension / Inflamation / Olmesartan medoxomil / Protein profile 1300 Proteomics Clin. Appl. 2008, 2, 1300–1312 1 Introduction Angiotensin II receptor blockers (ARBs) are a class of anti- hypertensive agents that inhibit the AT-1 subpopulation of angiotensin II receptors. In hypertensive patients, several randomized trials have documented beneficial effects of ARBs on cardiovascular disease morbidity and mortality [1– 3]. These trials have also raised the possibility that ARBs may Correspondence: Dr. Antonio José López Farré, Cardiovascular Research Unit of the Cardiology Department, Cardiovascular Institute, Hospital Clínico San Carlos, C/. Profesor Martín Lagos s/n. CP: 28040, Madrid, Spain E-mail: lcarinv.hcsc@salud.madrid.org Fax: 134-91-330-3692 Abbreviations: ARBs, angiotensin II receptor blockers; DBP , dia- stolic blood pressure; hsCRP , high-sensitive C-reactive protein; IL-6, interleukin-6; LDL, low density lipoprotein; SBP, systolic blood pressure * Dr. M. Luque { died during the preparation of the manuscript DOI 10.1002/prca.200700021  2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.clinical.proteomics-journal.com