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
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2
0
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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
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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
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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)