Chinese Medical Journal 2010;123(21):3123-3126
Levels of soluble adhesion molecules in patients with various
clinical presentations of coronary atherosclerosis
LU Hui-he, SHENG Zheng-qiang, WANG Yi and ZHANG Li
Keywords: vascular cell adhesion molecule-1; intercellular adhesion molecule-1; E-selectin; P-selectin;
coronary artery disease; inflammation
Background Adhesion molecules play an important role in the development and progression of coronary
atherosclerosis. The aim of this study was to compare concentrations of soluble forms of adhesion molecules in patients
with different clinical presentations of coronary artery disease (CAD).
Methods One hundred and twenty-eight patients with CAD were divided into three groups; the first group was acute
myocardial infarction group (AMI group, n=45), the second group was unstable angina pectoris group (UAP group, n=48),
the third group was stable angina pectoris group (SAP group, n=35). We compared them with patients with normal
coronary arteries (control group, n=31). The serum levels of vascular cell adhesion molecule (VCAM-1), intercellular
adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were measured in all subjects.
Results The serum level of VCAM-1 in the AMI group was significantly higher than in the UAP, SAP and control groups
(P <0.01). The level in the UAP group was significantly higher than the SAP group and control group (P <0.01) and the
level in the SAP group was significantly higher than in the control group (P <0.01). The serum ICAM-1 level was
significantly elevated in the AMI, UAP and SAP groups as compared to the control group (P <0.01). The levels of serum
E-selectin and P-selectin in the AMI and UAP groups were significantly higher than in the SAP and control groups (P
Conclusions Increased levels of VCAM-1 and ICAM-1, E-selectin and P-selectin, as markers of inflammation, showed
the importance of inflammatory processes in the development of atherosclerosis and clinical expression of CAD. Soluble
ICAM-1, VCAM-1, E-selectin and P-selectin concentrations are useful indicators of the presence of atherosclerosis and
the severity of CAD clinical presentation.
Chin Med J 2010;123(21):3123-3126
nflammation, in which adhesion molecules play an
important role, has been implicated in the pathogenesis
of atherosclerosis.1-4 Cellular adhesion molecules mediate
the margination, adhesion and transendothelial migration
of circulating mononuclear cells from the blood stream to
the extravascular compartment and have an important
role in the progression of atherosclerotic plaque.5,6 In
addition, adhesion molecules and various other cytokines
recruit and activate mononuclear cells to release matrix
metalloproteinases, promoting plaque rupture and the
initiation of acute coronary syndromes. Vascular cell
adhesion molecule-1 (VCAM-1) and intercellular
adhesion molecule-1 (ICAM-1) expressed by leukocytes
and platelets as endothelial integrin ligands, mediate the
adhesion and migration of leukocyte in endothelium, and
they are seldom expressed in normal coronary arteries.
Selectins, including E-selectin and P-selectin, are
involved in the first step of leukocyte adhesion at sites of
inflammation or injury. Their presence is characterized by
rolling and tethering of leukocytes to the endothelial
surface, to platelets or to other leukocytes.7
Soluble forms of adhesion molecules are detected in
human plasma and found to be elevated in various
inflammatory disorders.8-10 Elevated levels of soluble
adhesion molecules were also reported in patients with
acute and chronic coronary syndromes, but with
conflicting results.11-13 As a result, the pathologic roles of
different soluble adhesion molecules in various stages of
coronary artery disease (CAD) are not fully defined.
Clinical studies are still limited, and most of the studies
evaluated only one or two soluble adhesion molecules.
Therefore, we measured serum levels of VCAM-1,
ICAM-1, E-selectin and P-selectin in patients with acute
myocardial infarction (AMI), unstable angina pectoris
(UAP) and stable angina pectoris (SAP) and compared
them with patients with normal coronary arteries.
From January 2004 to December 2007, there were 128
in-patients with coronary artery atherosclerosis in our
department. According to the clinical diagnosis and
Department of Cardiology, The Second Affiliated Hospital, Nan
Tong University, Nantong, Jiangsu 226601, China (Lu HH, Sheng
ZQ, Wang Y and Zhang L)
Correspondence to: Dr. LU Hui-he, Department of Cardiology, The
Second Affiliated Hospital, Nan Tong University, Nantong, Jiangsu
226001, China (Tel: 86-513-85061272. Fax: 86-513-85507305.
Chin Med J 2010;123(21):3123-3126
Table 1. Clinical characteristics of the patients
SAP group Control
Age (mean±SD) (years)
57.4±2.6 56.8±2.158.3±1.9 55.6±2.20
Male (n (%))
36 (80%) 39 (81%)27 (77%) 24 (77%)0
Diabetes (n (%))
16 (36%) 19 (40%)11 (31%) 6 (19%)0
Hypertension (n (%))
22 (49%) 25 (52%)14 (40) 79 (23%)0
Smoker (n (%))
24 (53%) 29 (60%)18 (51%) 14 (45%)0
Hypercholesterolemia (n (%))
20 (44%) 22 (46%)15 (43%) 13 (42%)0
Weight mass index
25.7±2.1 24.6±2.225.1±2.6 23.9±1.80
1 lesion (n (%))
18 (40%) 20 (42%)15 (43%) 0
2 lesions (n (%))
15 (33%) 19 (40%)13 (37%) 0
3 lesions (n (%))
11 (24%) 10 (21%)9 (26%) 0
coronary angiography, the patients were divided into
three groups. The first group included 45 patients with
referred to the related AMI
AMI: the selected cases
diagnostic criteria in universal definition of myocardial
infarction.14 The second group included 48 patients with
UAP: the patients had resting chest pain in 48 hours, their
ECG manifested temporary ST segment depression or T
wave inversion, low flat or pseudo normal and the cTNI
level was normal. The third group included 35 patients
with SAP: the patients had typical labor chest pain, no
resting angina pectoris, with more than two months
history. The fourth group of 31 patients were the control
g typical ch
. All the coro
coronary angiography or
Excluding criteria were acute or chronic inflammation,
roup: patients with un
est pain, and normal
patients were given
tumor, hepatic or nephritic dysfunction, connective tissue
disease, or peripheral arterial.
Blood specimens and adhesion molecule measurement
Venous blood samples from the antecubitial vein were
drawn by needle aspiration in patients with AMI and UAP
before the initiation of antiplatelet therapy. In the SAP
group and in controls, blood samples were collected at the
time of clinical admission. The initial 4 ml of venous
blood was discarded, and a subsequent 5 ml was drawn.
All samples were centrifugated at 3000 r/min for 10
minutes and serum then stored at −40°C for subsequent
analysis. Serum levels of adhesion molecules (VCAM-1,
ICAM-1, E-selectin and P-selectin) were measured by
commercially available enzyme-linked immunosorbent
assay kits according to the manufacturer’s instructions (R
Chinese Medical Journal 2010;123(21):3123-3126
＆D Syntems, Inc., USA).
arametric data. Continuous variables
percentages for nonp
ere compared by means of one-way analysis of variance
(one-way ANOVA). Differences in nonparametric data
were compared using χ2 test. A P-value ≤0.05 was
considered statistically significant. The SPSS 13.0
statistical software package was used for all calculations.
Clinical characteristics of the patients
There were no significant differences in sex, age, or risk
factors among the four groups. The narrow coronary
numbers (stenosis ≥50%) among the AMI, UAP, SAP
groups were not significantly different (Table 1).
Serum soluble adhesion molecule levels
As shown in Table 2, the serum level of VCAM-1 in the
AMI group was significantly higher than in the UAP,
SAP and control groups (P <0.01); the level in the UAP
group was significantly higher than in the SAP and
control groups (P <0.01); and in the SAP group
significantly higher than in the control group (P <0.01).
There were no significant differences of serum ICAM-1
level between the AMI, UAP and SAP groups. However,
the serum ICAM-1 level was significantly elevated in
those groups compared to the control group (P <0.01).
The level of E-selectin in the AMI group was not
t from that in the UAP group; but the
in the SAP and
een the w
For P-selectin, no significant difference was observed
between the AMI and UAP groups, however, P-selectin
was significantly higher in the AMI and UAP groups
compared to the SAP and control groups (P <0.01). The
vel of P-selectin in the SAP group le
higher than in the control group (P <0.01).
dhesion molecules play an important role inA
pathphysiological process of atherosclerosis. This study
showed that the VCAM-1 serum levels among AMI, UAP,
SAP and control groups had significant differences. The
level was the highest in the AMI group and the second
highest in the UAP group. Therefore, VCAM-1 may be
nvolved in the atherosclei
d rupture and th
the aggregation of leukocytes. The elevation of leukocyte
count may have some connection with the high level of
VCAM-1 expression seen within two hours of an AMI
occurrence.1,5 The interaction between endothelial cells
and leukocytes plays a crucial role in acute myocardial
infarction: the premise of leukocyte mediated injury is
t leukocyte tha s adhere to vascular endothelial cells and
lead to endothelium dysfunction.15 In this study the
oluble adhesion molecules
rosis plaque progression,
zation and related to
eterioration and even
expressed mainly in
Table 2. Serum levels of s
selectin in A
as no s
UAP groups we
r ence beti
Chin Med J 2010;123(21):3123-3126
Data are expressed as mean±SD. *P <0.01 vs. control gr
VCAM-1 level in AMI was much higher than in non-ST
elevation acute coronary syndro
me and stable angina.
This might be the results of leukocyte-mediated
myocardial damage from myocardial ischemia or necrosis.
It had been found that the VCAM-1 levels in coronary
heart disease (CHD) patients who had myocardial
ischemia events were significantly higher than in patients
without ischemic events. Furthermore, the VCAM-1
levels were closely related to future CHD cardiac
events.16 Further studies are needed to observe the exact
process of soluble adhesion molecules in myocardial
In this study, there were no significant differences of
ICAM-1 levels among the AMI, UAP and SAP groups,
but the ICAM-1 levels were significantly higher in those
groups than in the control group. This indicates that the
ICAM-1 level could be used as a junior marker of
vascular inflammation in coronary atherosclerosis, but it
had nothing to do with the instability of coronary
plaque.17 Compared with other adhesion molecules,
ICAM-1 is distributed more broadly among tissues and
cells. It is expressed on endothelial cells, hematopoietic
cells, epithelial cells, secular smooth muscle cells, and
fibroblasts, which might result in the similar ICAM-1
serum levels found in the AMI, UAP, and SAP groups.
E-selectin, a sign of endothelial cell activity is mainly
expressed on the endothelial cell surface.10 The plasma
E-selectin in AMI was higher than in the SAP and control
groups, but there was no difference between the SAP and
control groups.11 E-selectin levels in UAP was
significantly higher than in the SAP and control groups.12
In this study, the E-selectin levels in the AMI and UAP
groups were significantly higher than in the SAP and
control groups, but there was no difference between the
SAP and control groups. All these studies showed that the
elevation of E-selectin reflected the inflammation
associated with acute coronary syndrome and myocardial
AMI, UAP, and sudden cardiac death have a close
relation with arterial plaque rupture and coronary
thrombus. Therefore, platelet activation is the premise of
acute coronary syndrome. In t
activation, such as P-selectin, may r
coronary atherosclerosis. This study results are in
accordance with the previous research finding that
P-selectin levels in AMI and UAP patients are
significantly higher than in the SAP and control groups.
However, in this study, P-selectin in SAP patients was
significantly higher than in the control group. Although
the exact mechanism was unclear, the elevation of
P-selectin in SAP may be the result of junior artery
inflammation and platelet activation.19
VCAM-1, ICAM-1, E-selectin, P-selectin have different
levels in different types of CHD. Measurement of
VCAM-1, E-selectin and P-selectin have an important
value in judging the instability of coronary plaque.
This study had a small sample and it focused on adhesion
molecules from the peripheral blood but not from
coronary sinus. It is necessary to carry out further studies
to clarify the role of adhesion molecules in acute or
chronic coronary syndrome.
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(Received April 29, 2010)
Edited by WANG De