Serum levels of osteopontin predict major adverse cardiovascular events in patients with severe carotid artery stenosis

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:255

Article

Carbone, Federico¹  Rigamonti, Fabio²  Burger, Fabienne³  Roth, Aline³  Bertolotto, Maria¹  Spinella, Giovanni⁴  Pane, Bianca⁴  Palombo, Domenico⁴  Pende, Aldo¹  Bonaventura, Aldo¹  Liberale, Luca^1,5  Vecchie, Alessandra¹  Dallegri, Franco^1,6  Mach, Francois^2,3  Montecucco, Fabrizio^1,6,7 

[1] Univ Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 Viale Benedetto 15, I-13132 Genoa, Italy

[2] Geneva Univ Hosp, Dept Med Specialties, Div Cardiol, 4 Rue Gabrielle Perret Gentil, CH-1211 Geneva, Switzerland

[3] Univ Geneva, Div Cardiol, Dept Med Specialties, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland

[4] Osped Policlin San Martino, Vasc & Endovasc Surg Unit, Dept Surg, 10 Largo Benzi, I-16132 Genoa, Italy

[5] Univ Zurich, Ctr Mol Cardiol, 12 Wagistr, CH-8952 Schlieren, Switzerland

[6] Osped Policlin San Martino, 10 Largo Benzi, I-16132 Genoa, Italy

[7] Univ Genoa, CEBR, 9 Viale Benedetto 15, I-16132 Genoa, Italy

关键词: Atherosclerosis;    Osteopontin;    Macrophage;    Inflammation;   

DOI  :  10.1016/j.ijcard.2018.01.008

来源: Elsevier

【 摘 要 】

Background: Inflammatory mediators in the blood stream and within plaques are key determinants in atherogenesis. Here, we investigated serum osteopontin (OPN) as a potential predictor of poor outcome in patients with severe carotid atherosclerosis. Methods: Carotid plaques and serum were collected from patients asymptomatic (n = 185) or symptomatic (n = 40) for ischemic stroke. Plaques were stained for lipids, smooth muscle cells, neutrophils, M1 and M2 macrophage subsets and matrix metallopropteinase-9 (MMP-9). Serum levels of OPN and interleukin-6 (IL-6) were determined by colorimetric enzyme-linked immunosorbent assays. Results: Symptomatic patients showed a two-fold increase in serum OPN levels. In both symptomatic and asymptomatic patients, OPN levels positively correlated with intraplaque count of neutrophils, total macrophages, and MMP-9 content. In asymptomatic patients, OPN levels also positively correlated with lipids and M1 macrophage subsets. Receiver operating characteristic curve analysis identified serum OPN concentration of 70 ng/ml as the best cut-off value to predict major adverse cardiovascular events (MACEs). Patients with high OPN levels had more vulnerable plaque phenotype and reduced levels of HDL-cholesterol and IL-6 as compared to low OPN levels. Kaplan-Meier curve confirmed that patients with OPN levels > 70 ng/ml had more MACEs at a 24-month follow-up. In the multivariate survival analysis, OPN levels > 70 ng/ml predicted MACEs, independently of age, gender, and symptomatic status. Conclusion: High circulating OPN levels were strongly correlated with vulnerability parameters within plaques and predict MACEs in patients with severe carotid artery stenosis. Although confirmation is needed from larger trials, OPN could be a promising clinical tool to assess atherosclerotic outcomes. (c) 2018 Elsevier B.V. All rights reserved.

【 授权许可】

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