683 © Schattauer 2011 Thrombosis and Haemostasis 106.4/2011 Platelets and Blood Cells Increased levels of platelet activation markers are positively associated with carotid wall thickness and other atherosclerotic risk factors in obese patients Éva Csongrádi 1,2 ; Béla Nagy Jr 3 ; Tibor Fulop 4 ; Zsuzsa Varga 1 ; Zsolt Karányi 1 ; Mária T. Magyar 5 ; László Oláh 5 ; Mária Papp 6 ; Andrea Facskó 7 ; János Kappelmayer 3 ; György Paragh 1 ; Miklós Káplár 1 1 1 st Department of Medicine, Medical and Health Science Center, University of Debrecen, Hungary; 2 Department of Physiology & Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA; 3 Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Hungary; 4 Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, Mississippi, USA; 5 Department of Neurology, Medical and Health Science Center, University of Debrecen, Hungary; 6 2 nd Department of Medicine, Medical and Health Science Center, University of Debrecen, Hungary; 7 Department of Ophthalmology, Medical and Health Science Center, University of Debrecen, Hungary Summary The role of platelets in the development of atherosclerosis and obesity- related prothrombotic state is still under investigation. In this cross-sec- tional cohort study, we measured the levels of different platelet acti- vation markers and evaluated their relationship with carotid intima- media thickness (IMT) along with other atherosclerotic risk factors in obese patients with or without atherosclerotic co-morbidities. We en- rolled 154 obese patients, including 98 with either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin ex- pression and the number of platelet-derived microparticles (PMPs) were measured by flow cytometry; soluble P-selectin levels were ana- lysed by ELISA and Thr715Pro P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by ultrasonography. The levels of platelet activation parameters were significantly elevated in all obese subjects with increased carotid IMT compared to healthy con- Correspondence to: Éva Csongrádi, MD 2500 North State Street Jackson, MS 39216, USA Tel.: +1 601 815 4882, Fax: +1 601 984 1833 E-mail: ecsongradi@umc.edu or csongradi69@gmail.com trols. There was no effect of Thr715Pro genotype on soluble P-selectin levels in obese individuals contrary to normal subjects. Significant and positive association was revealed between carotid IMT and platelet P-selectin (p<0.0001), soluble P-selectin (p=0.039) and PMP (p=0.0001) levels. After adjusting for multiple variables, independent association was found between soluble P-selectin and fibrinogen (p=0.007), PMP levels and body mass index (p<0.0001) as well as pla- telet P-selectin and carotid IMT (p=0.012) plus plasminogen activator inhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showed positive associations with abnormal carotid IMT and other risk factors in obesity suggesting a critical role of enhanced platelet reactivity in atherosclerotic wall alteration. Keywords Atherosclerosis, platelets, carotid intima-media thickness, P-selectin, microparticles, obesity, Thr715Pro polymorphism Financial support: This work was supported by a “Mecenatura” grant of Dr. Miklós Káplár (University of Debrecen, Hungary), by an OTKA grant (K75199) of Dr. János Kappelmayer, and by the TAMOP 4.2.1/B-091/1/KONV-2010-0007 project to Dr. János Kappelmayer. Received: January 18, 2011 Accepted after minor revision: June 18, 2011 Prepublished online: August 25, 2011 doi:10.1160/TH11-01-0030 Thromb Haemost 2011; 106: 683–692 Introduction Enhanced platelet activation has been shown to occur in a number of diseases with atherosclerosis such as coronary artery disease (1–3), cerebrovascular disease (4, 5) and type 2 diabetes mellitus (DM) (6, 7); however, only limited data are available in terms of obesity. Previous studies demonstrated that activated platelets played a functional role in the initiation of atherosclerosis in mice (8, 9). Furthermore, co-morbidities like hypertension, hypergly- caemia or dyslipidaemia are additional major risk factors for atherosclerotic disease associated with platelet hyperactivity in hu- mans (10–12). Activated platelets induce P-selectin (CD62) ex- pression, an adhesive membrane glycoprotein from α-granules re- sulting in transient attachment of platelets to leukocytes and en- dothelial cells during atherothrombotic and inflammatory pro- cesses (13). In the meantime, secreted soluble P-selectin circulates at an increased level in the plasma and is involved in further cellu- lar interactions (14). Microparticles are small membrane particles shed from activated blood cells and endothelial cells promoting coagulation and inflammation via their procoagulant surface properties (15). Elevated numbers of platelet-derived micropar- ticles (PMPs) were found in vascular diseases and type 2 DM (16). Abnormalities in the coagulation processes with higher levels of prothrombotic factors (17) and enhanced levels of platelet acti- For personal or educational use only. No other uses without permission. All rights reserved. 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