Cardiovascular Journal of Africa: Vol 22 No 6 (November/December 2011) - page 25

CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 6, November/December 2011 AFRICA 315
arteries for detection of SDF-1a and CXCR4 mRNA with
RT-PCR. Results showed the expression of SDF-1a mRNA in
groups S and A was detectable immediately after injury, followed
by a gradual decrease, but it was undetectable one month later.
Administration of a CXCR4 antagonist seemed to have no effect
on expression of SDF-1a mRNA (Fig. 1).
However, the expression of CXCR4 mRNA was detected four
days after injury and continued for one month (Fig.1). AMD3100
is an antagonist of CXCR4, which inhibits the interaction
between SDF-1a and CXCR4, so the expression of CXCR4
mRNA was decreased in group A compared with that in group
S (Fig. 2).
Western blot assay was performed to evaluate the expression
of CXCR4 protein in the arteries. As shown in Fig. 3, the expres-
sion of CXCR4 protein was reduced immediately after injury,
followed by a gradual increase and it lasted for three months.
Results also indicated the expression of CXCR4 protein in group
S was markedly higher than in group A.
Spatial localisation of CXCR4 in the injured common carotid
artery was determined by immuno-histochemical assay (Fig. 4).
CXCR4-positive staining was observed in the neo-intima of the
common carotid artery (Fig. 4A, B). The positive staining in
group S was noted as early as one day after injury, followed by
a gradual increase. However, in group A, it was delayed to four
days after injury, with low intensity of staining, when compared
with that in group S. CXCR4 expression no longer appeared
after three months in either group S or A.
The rat carotid artery sections one day, one month and three
months after balloon injury from groups S and A were evaluated
for carotid artery stenosis. After H&E staining, the sections were
detected with the Image 45 pro analysis program to measure the
extent of arterial intimal hyperplasia. It was found that, after one
and three months, vascular intimal hyperplasia in groups S and A
was significantly higher than in the control group (p < 0.05 and
0.01). The degree of intimal hyperplasia in group A was lower
than in group S after one month (p < 0.05), and the difference
between the two groups remained after three months (p < 0.05)
(Table 3, Fig. 5).
Discussion
Coronary heart disease is one of the commonest causes of death.
Since the use of PTCA in the treatment of coronary athero-
sclerosis, numerous patients with coronary heart disease have
benefited from PCI, but the relatively high incidence of resteno-
sis after PCI has been a major problem, despite the short-term
success of this technique. So far, no effective treatment strategies
have been successful in preventing restenosis after PCI. Studies
have demonstrated that excessive proliferation of the neo-intima
plays a critical role in restenosis. Therefore, appropriate inhibi-
tion of neo-intimal proliferation may be a promising strategy in
the prevention of restenosis.
Proliferation of stem/progenitor cells occurs following tissue
ischaemia or damage such as acute myocardial infarction.4 Many
cells may migrate into the ischaemic region to participate in
tissue repair and angiogenesis.7,8 So far, the mechanisms under-
lying the progenitor cell migration to the injured site are poorly
understood. Recently, stem or progenitor cell therapy has been
a treatment choice for the improvement of neovascularisation
and left ventricular function following acute myocardial infarc-
tion. Various types of stem cells and progenitor cells have been
successfully used in the experimental acute myocardial infarc-
TABLE 1. PERIPHERAL CXCR4+CD34 + CELLSAFTER INTIMAL INJURY (x ± SD, n = 12 PER GROUP)
Group C
Group S Group A
S0 S1d S4d S7d S1m S3m A0 A1d A4d A7d A1m A3m
CXCR4 +CD34+ cells 0.021 ±
0.002
1.260 ±
0.003**
0.729 ±
0.019**
0.187 ±
0.004**
0.019 ±
0.004
0.022 ±
0.001
0.020 ±
0.038
1.411 ±
0.021**#
0.889 ±
0.012** #
0.185 ±
0.005**
0.023 ±
0.004
0.022 ±
0.011
0.019 ±
0.055
**p < 0.01 vs group C; #p < 0.05 vs group S; d = day; m = month.
TABLE 2. PLASMA LEVEL OF SDF-1a AFTER INTIMAL INJURY (x ± SD, ng/ml, n = 12 PER GROUP)
Group C
Group S Group A
S0 S1d S4d S7d S1m S3m A0 A1d A4d A7d A1m A3m
SDF-1<alpha> (ng/ml) 0.312 ±
0.006
0.885 ±
0.022*
1.328 ±
0.009*
1.119 ±
0.013*
0.323 ±
0.005
0.320 ±
0.006
0.309 ±
0.056
0.855 ±
0.024*
1.191 ±
0.039*
1.083 ±
0.004*
0.324 ±
0.056
0.319 ±
0.012
0.303 ±
0.027
*p < 0.01 vs group C.
Fig. 1. Expression of SDF-1 a mRNA (381 bp) in an injured
common carotid artery.
S4d A4d S1d A1d marker S1m A1m S3m A3m S7d A7d
S0 A0 marker C
Fig. 2. Expression of CXCR4 mRNA (267 bp) in an injured
common carotid artery.
marker S0 A0 S1d S4d A4d A1d
C A 7d S7d A1m S1m marker A 3m S3m
Fig. 3. Expression of CXCR4 protein (67 kd) in an injured
common carotid artery.
A4d S4d A7d S7d marker C S1m A1m S3m A3m
Marker A1d S1d A0 S0