Relationship between toll-like receptor 4 levels in aorta and severity of atherosclerosis

Journal of International Medical Research, Aug 2014

Objective To investigate the relationship between levels of toll-like receptor 4 (TLR4) protein in aortic tissue and the severity of atherosclerosis in patients undergoing coronary artery bypass graft (CABG) surgery.

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Relationship between toll-like receptor 4 levels in aorta and severity of atherosclerosis

Shanshan Xing 0 3 Fei Zheng 0 2 Wei Zhang 0 1 Dong Wang 0 4 Qichong Xing 0 2 0 >> Version of Record - Jul 10, 2014 OnlineFirst Version of Record - Jun 12, 2014 What is This? 1 Department of Endocrinology, Qianfoshan Hospital, Shandong University , Jinan, China 2 Department of Cardiology, Qianfoshan Hospital, Shandong University , Jinan, China 3 Department of Internal Medicine, Shandong University of Traditional Chinese Medicine , Jinan, China 4 Department of Cardiovascular Disease, Qianfoshan Hospital, Shandong University , Jinan, China - Relationship between toll-like receptor 4 levels in aorta and severity of atherosclerosis Journal of International Medical Research 2014, Vol. 42(4) 958965 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0300060514534645 imr.sagepub.com Abstract Objective: To investigate the relationship between levels of toll-like receptor 4 (TLR4) protein in aortic tissue and the severity of atherosclerosis in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: Samples of ascending aorta and renal artery were collected from patients undergoing CABG surgery or kidney donation, respectively. TLR4 levels were determined by immunohistochemistry. Coronary angiography was performed to determine atherosclerosis severity via Gensini score. Results: TLR4 was present at high levels in aortic tissues from patients (n 46), and was absent from renal artery tissue (controls; n 11). There was a significant positive correlation between Gensini score and TLR4 level in the patient group. Conclusions: TLR4 may play an important role in atherosclerosis and could be a potential therapeutic target for treatment of coronary artery disease. Discarded aortic tissue obtained during CABG surgery provides a new approach to the study of the pathogenesis of atherosclerosis. Introduction The response-to-retention hypothesis is widely accepted to explain the pathogenesis of atherosclerosis.13 This hypothesis states that lipoproteins (mainly low-density lipoprotein [LDL]) are retained in the intima of arteries under certain conditions and are oxidatively modified by the extracellular matrix. These oxidized lipoproteins Creative Commons CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permisDsoiownnlopardoevdidfreodmtihmer.soargiegpinuabl.cwomorbkyigsuaetsttroibnuOtcetdobaesr 1s6p,e2c0if1i4ed on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm). stimulate the transformation of monocytes to macrophages that then convert to foam cells by phagocytosis of oxidized LDL, resulting in local vascular nonadaptive inflammation.47 Toll-like receptors (TLRs) are pathogen recognition receptors present on the surface of mammalian somatic cells.8 TLRs are closely related to the innate immune system; they initiate signalling pathways within cells and activate the immune response by recognizing specific structures that are shared by pathogens but not by host cells.911 To date, 13 members of the TLR family have been identified, of which TLR4 is closely linked to atherosclerosis.12 The aim of the current study was to investigate the relationship between levels of TLR4 in aortic tissue and the severity of atherosclerosis in patients who underwent coronary artery bypass graft (CABG) surgery. Patients and methods Study population The study enrolled patients scheduled to undergo CABG surgery at Qianfoshan Hospital, Jinan, China, between September 2012 and September 2013. Indications for CABG included: unstable angina with medication failure; disease of the left main coronary artery or the bifurcate part of arteries; disease of all coronary vessels, especially combined with cardiac dysfunction or diabetes; disease of two coronary vessels, combined with high-grade stenosis of proximal left anterior descending artery; (v) disease with percutaneous coronary intervention failure. Exclusion criteria were: aged <18 years; concomitant valvular surgery or MAZE procedures. Samples of ascending aortic tissue were collected during surgery. Healthy subjects who were donating a kidney to a blood relative were recruited as controls, and provided renal artery tissue free from atherosclerotic lesions. Data regarding body mass index (BMI), smoking status, hypertension (blood pressure 140/ 90 mmHg) and diabetes mellitus were obtained from all participants. The Ethics Committee of Qianfoshan Hospital, Jinan, China, approved the study, and all subjects provided written informed consent prior to enrolment. Laboratory analyses Peripheral blood was taken from all study participants 1 day after enrolment following an overnight fast. Blood (20 ml) was drawn into tubes containing anticoagulant (sodium citrate, 3.2%), mixed, centrifuged ( 4 C (...truncated)


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Shanshan Xing, Fei Zheng, Wei Zhang, Dong Wang, Qichong Xing. Relationship between toll-like receptor 4 levels in aorta and severity of atherosclerosis, Journal of International Medical Research, 2014, pp. 958-965, 42/4, DOI: 10.1177/0300060514534645