4-Methoxyphenyl (E)-3-(Furan-3-yl) Acrylate Inhibits Vascular Smooth Muscle Cell Proliferation

Article abstract of DOI:10.1097/FJC.0000000000000831

The Cordyceps extract exhibits antiproliferative potential in vascular smooth muscle cells (SMCs) through the mitogen-activated protein kinase signaling pathway. In this study, we aimed to identify the active compounds in the Cordyceps extract and analyze their role in remodeling the arterial wall. On investigation, we discovered the following active compound: 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate and synthesized it. We performed antiproliferation and antimigration assays in addition to an in vivo vessel wall remodeling experiment. Investigation of the mechanism adopted by the active compound to remodel the vessel was performed. The newly synthesized compound inhibited the proliferation and migration of SMCs. Treatment with the synthesized compound reduced neointima formation in the balloon-injured Sprague-Dawley rat model. In addition, this compound inhibited the activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in type I collagen-activated SMCs. Moreover, this compound suppressed the expression of cycloxygenase-2 (COX-2) in SMCs. Therefore, this compound can exert potential antiarteriosclerotic effects by modulating vessel wall remodeling. In conclusion, the newly synthesized 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alternative therapeutic intervention for the treatment of atherosclerosis.

Full text of DOI:10.1097/FJC.0000000000000831

ORIGINAL ARTICLE
4-Methoxyphenyl (E)-3-(Furan-3-yl) Acrylate Inhibits
Vascular Smooth Muscle Cell Proliferation
Seongho Han, MD,* Mina Son, MS,† Yunmi Lee, PhD,‡ Sae Hee Cheon, PhD,§ and Sung-Whan Kim, PhD†
calcium, cellular waste products, and fibrin are the main
Abstract: The Cordyceps extract exhibits antiproliferative potential
in vascular smooth muscle cells (SMCs) through the mitogen-
activated protein kinase signaling pathway. In this study, we aimed
to identify the active compounds in the Cordyceps extract and ana-
lyze their role in remodeling the arterial wall. On investigation, we
discovered the following active compound: 4-methoxyphenyl (E)-3-
(furan-3-yl) acrylate and synthesized it. We performed antiprolifera-
tion and antimigration assays in addition to an in vivo vessel wall
remodeling experiment. Investigation of the mechanism adopted by
the active compound to remodel the vessel was performed. The
newly synthesized compound inhibited the proliferation and migra-
tion of SMCs. Treatment with the synthesized compound reduced
neointima formation in the balloon-injured Sprague–Dawley rat
model. In addition, this compound inhibited the activation of matrix
causes for the plaque buildup inside the arteries. The major
sources of plaque are vascular smooth muscle cells (SMCs)
and the extracellular matrix (ECM), and SMCs contribute to
numerous processes in atherosclerosis.1 In addition, it has
been reported that there is a close relationship between reste-
nosis and SMC proliferation in the intimal layer.2
It is well known that Cordyceps are ethno-
pharmacologically valuable mushrooms and widely used as
traditional medicine or tonics in Asian countries. Cordyceps
display potent anticancer, anti-inflammatory, antiviral, antiox-
idative, antidiabetic, antinociceptive, and antiobesity pharma-
cological properties.3,4 Several pharmaceutical effects of the
active components of the extract or KTH-13 [4-isopropyl-2,6-
bis(1-phenylethyl) phenol] derived from artificially cultivated
Cordyceps have been reported.5–7
metalloproteinase-2 and matrix metalloproteinase-9 in type
I
collagen-activated SMCs. Moreover, this compound suppressed the
expression of cycloxygenase-2 (COX-2) in SMCs. Therefore, this
compound can exert potential antiarteriosclerotic effects by modu-
lating vessel wall remodeling. In conclusion, the newly synthesized
4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alternative
therapeutic intervention for the treatment of atherosclerosis.
In this study, we extracted 4-methoxyphenyl (E)-3-(furan-
3-yl) acrylate from the Cordyceps extract and synthesized it. In
addition, we investigated the activity of this compound in vessel
remodeling and its underlying mechanism. Pharmaceutical
activities of 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might
highlight a potential therapeutic intervention for atherosclerosis.
Key Words: 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate,
Cordyceps, proliferation, vascular smooth muscle cells
MATERIALS AND METHODS
(J Cardiovasc Pharmacolꢀ 2020;76:106–111)
Preparation of Compounds 1, 2, and 3 and
Analysis of Structure
INTRODUCTION
To a solution of (E)-3-(3-furyl) prop-2-enoic acid (1,
100 mg, 0.724 mmol), 4-methoxyphenol (2, 180 mg,
1.45 mmol) and dimethylamino pyridine (106 mg,
0.869 mmol) in CH2Cl2 (0.7 mL) were added to dicyclohexyl
carbodiimide (224 mg, 1.09 mmol) at room temperature. The
mixture was allowed to reflux and was stirred overnight. The
resulting solution was allowed to cool to room temperature
and filtered through a short pad of silica gel while washing
with Et2O. The filtrate was concentrated in vacuo, and the
resulting crude product was purified using silica gel column
chromatography to obtain the desired 4-methoxyphenyl (E)-
3-(furan-3-yl)acrylate (3, 140 mg, 0.573 mmol, 79%) as
a white solid (Fig. 1). This compound has been previously
reported and spectra data match described.8 1H NMR spectra
were recorded on a JEOL JNM-AL400 (400 MHz) spectrom-
eter. Chemical shifts are reported in parts per million from
tetramethylsilane, with solvent resonance as the internal stan-
dard (CDCl3: d 7.27 ppm) (see Figure S1, Supplemental
Digital Content 1, http://links.lww.com/JCVP/A459). Data
are reported as follows: chemical shift, multiplicity (s =
Atherosclerosis is a disease characterized by the
narrowing and hardening of arterial intima. Fat, cholesterol,
Received for publication December 5, 2019; accepted February 28, 2020.
From the *Department of Family Medicine, College of Medicine, Dong-A
University, Busan, Republic of Korea; †Department of Medicine,
Catholic Kwandong University College of Medicine, Gangneung,
Republic of Korea; ‡Department of Chemistry, Kwangwoon University,
Seoul, Republic of Korea; and §Department of Dental Hygiene, Masan
University, Masan, Korea.
This work was financially supported through National Research Foundation
of Korea (NRF) grants funded by the Korean Government (No. NRF-
2016R1A2B4012683 and No. NRF-2015M3A9E6029558) and research
funds of Dong-A University and Catholic Kwandong University.
The authors report no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF
versions of this article on the journal’s Web site (www.jcvp.org).
Reprints: Sung-Whan Kim, PhD, Department of Medicine, Catholic
Kwandong University College of Medicine, 25, Simgok-ro 100 beon-
gil, Seo-gu International St. Mary’s HospitalIncheon, Korea 404-190
(e-mail: swkim@cku.ac.kr).
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J Cardiovasc Pharmacolꢁ Volume 76, Number 1, July 2020
Vascular Smooth Muscle Cell Proliferation
singlet, d = doublet, t = triplet, q = quartet, quint = quintet,
and m = multiplet), coupling constants (Hz), and integration.
13C NMR spectra were recorded on a JEOL JNM-AL400
(100 MHz) spectrometer with complete proton decoupling.
Chemical shifts are reported in parts per million from tetra-
methylsilane, with solvent resonance as the internal standard
(CDCl3: d 77.00 ppm) (see Figure S2, Supplemental Digital
Content 1, http://links.lww.com/JCVP/A459).
(Sakura, Torrance, CA) and snap frozen in liquid nitrogen.
Then, tissues were sectioned into 10 mm thickness and
stained with hematoxylin and eosin (H&E). The stained tis-
sues were evaluated with light microscopy. Normal and ne-
ointimal areas were analyzed using NIH images.
Cell Migration Assay
Scratch wound assays were performed by a previously
reported method with modifications.9 SMCs were seeded to
a final density of 1 · 105 cells/well in a 6-well culture plate
and cultured to produce confluent monolayers at 378C in 5%
CO2. Then, confluent monolayers were scratched using
a pipette tip and cultured in low-glucose DMEM supple-
mented with 100-mg/mL streptomycin, 100-U/mL penicillin,
and 10% FBS as a control group. In addition, we cultured
SMCs in low-glucose DMEM supplemented with 100-mg/
mL streptomycin, 100-U/mL penicillin, and 10% FBS with
various concentrations of the compound for 24 hours.
Migrated cells were counted using NIH images.
Cell Culture
Rat aortic SMCs were purchased from Lonza
(Walkersville, MD). SMCs were cultured in Dulbecco’s mod-
ified Eagle’s medium (Life Technologies, Grand Island, NY)
supplemented with 10% fetal bovine serum (FBS) (Life
Technologies) in a 378C incubator at 5% CO2.
Cell Proliferation Assay
SMCs were plated in 96-well plates at 3 · 103 cells/well
and starved with 0.1% FBS for 24 hours and then treated with
various concentrations of the compound for 72 hours. After
treatment, cell proliferation was examined using a Cell
Counting Kit-8 (CCK-8) assay kit (Dojindo, Japan). CCK-8
allows sensitive colorimetric assays for the determination of
cell viability in cytotoxicity or cell proliferation assays. The
CCK-8 solution (10 mL) was treated to each well and incu-
bated for 2 hours at 378C. The absorbance was examined at
450 nm using a microplate reader.
Western Blotting
For the western blot analysis, cells were washed once
with PBS, and then, the protein was isolated using a lysis
buffer containing 150-mM NaCl, 1% Triton X-100, 0.1%
sodium dodecyl sulfate, 1% sodium deoxycholate, 50-mM
Tris/HCl, and 2-mM EDTA, with a protease inhibitor
cocktail. Protein concentrations were determined by a BCA
Protein Assay Kit (Thermo Scientific, Rockford, IL). Then,
equal amounts of protein were electrophoresed with 12%
sodium dodecyl sulfate–polyacrylamide gels, transferred to
nitrocellulose membranes, blocked using tris-buffered saline
with Tween 20 containing 5% (wt/vol) nonfat dried skim milk
powder for 1 hour at room temperature. Then, the membranes
were incubated with primary antibodies (1:1000) in a blocking
buffer overnight at 48C. The membranes were washed with
tris-buffered saline with Tween 20 for 10 minutes and then
treated with horseradish peroxidase–conjugated secondary
antibody at room temperature for 1 hour. Then, bands were
detected by the enhanced chemiluminescence western blot-
ting detection reagent. The expression levels were measured
using the Davinch-K western image system (Lab plus,
Neointima Formation Study
The animal experiment was approved by the Catholic
Kwandong University animal care committee. Balloon denu-
dation of the carotid artery endothelium was evoked in 4-
week-old male Sprague–Dawley rats (Daehan Biolink,
Chungbuk, Korea) as described in previous reports [5, 8]. In
brief, rats were anesthetized with ketamine (10 mg/kg) and
xylazine (5 mg/kg). A 2F Fogarty balloon catheter (Edwards
Lifesciences, Mississauga, ON) was inserted into the external
carotid branch to the aortic arch [5, 8]. Then, the catheter was
insufflated to produce slight resistance and withdrawn 3
times. Sham control was induced by the same operation with-
out balloon insertion. Vehicle (saline) or 0.05 mL of the
compound (20 mΜ) was injected daily intraperitoneally for
3 weeks after the balloon injury. We tested the toxicity of the
compound for concentration and dose in rats. We did not find
any signs of toxicity or change in body weight in rats for 4
weeks.
Korea). EMMPRIN (35 kDa, ab64616) and
b-actin (42
kDa, ab20272) antibodies were purchased from Abcam
(Cambridge, MA).
Reverse Transcription Polymerase Chain
Reaction and Analysis
Hematoxylin and Eosin Staining
Reverse transcription polymerase chain reaction (RT-
PCR) was conducted as reported previously.10 In brief, total
RNA was isolated using RNA-stat (Ambion, Austin, TX),
and extracted RNA was reverse-transcribed using TaqMan
Reverse Transcription Reagents (Perkin-Elmer Applied
Three weeks after the balloon injury, carotid arteries of
the Sprague–Dawley rats were harvested and fixed with 4%
paraformaldehyde. Within 12 hours after fixation, tissues
were embedded in the optimal cutting temperature compound
FIGURE 1. Procedure for the synthesis of 4-
methoxyphenyl (E)-3-(furan-3-yl) acrylate.
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Han et al
J Cardiovasc Pharmacolꢁ Volume 76, Number 1, July 2020
Biosystems, Foster City, CA). The synthesized cDNA was
subjected to RT-PCR using primers and probes. RNA tran-
script levels were quantitatively measured by an ABI Prism
7000 (Applied Biosystems, Foster City, CA). Relative mRNA
expression was normalized to GAPDH expression, and those
were calculated as described previously.11
SMCs were treated for 72 hours with several of the
synthesized compounds to examine their antiproliferative
effect. On analyzing the compounds, we observed that an
increased concentration of the 3-furanylacrylate derivative [4-
methoxyphenyl (E)-3-(furan-3-yl) acrylate: #14] significantly
decreased the extent of proliferation in SMCs, and over
50 mM of compound #14 markedly inhibited the proliferation
of SMCs by approximately 80% (Fig. 2).
RT-PCR Primers
The primers used for RT-PCR were as follows: matrix
metalloproteinase (MMP)-2, fwd 50-GCGGATCCAGC-
GCCCAGAGAGACAC-30, rev 50-TTAAGCTTCCAC TC-
CGGGCAGGATT-30, MMP-9, fwd 50-TGGACGATGC-
CTGCAA CGTG-30, rev 50- GTCGTGCGTGTCCAA-
AGGCA–30, COX-2, fwd 50-TCCAATCGCTGTACAA-
GCAG-30, rev 50 TCCCCAAAGATAGCAT CTGG-30;
GAPDH, fwd 50-CTCCCAACGTGTCTGT TGTG-30, and
rev 50-TGAGCTTGAC AAAGTGGTCG-30. GAPDH was
used for the internal standard.
In Vivo Antiatherosclerotic Effects in the
Balloon Injury Rat Model
To investigate the in vivo antiatherosclerotic effects, we
induced a balloon injury in the carotid artery of the rat model.
The effect of compound #14 on neointimal hyperplasia was
examined by histomorphometric analysis. The vehicle (PBS)-
treated group showed abundant neointimal hyperplasia due to
vascular injury at 3 weeks after the balloon injury. However,
20 mM of compound #14 injected intraperitoneally resulted in
a significant reduction of neointimal hyperplasia (Fig. 3).
Statistical Analysis
Effects of In Vitro SMC Migration
Statistical significance was determined by Student’s t
test and analysis of variance with Bonferroni’s multiple com-
parison tests using SPSS v12.0 software. All data were shown
as mean 6 SD from at least 3 independent experiments. Data
with P , 0.05 were considered statistically significant.
To examine the SMC migration effect of compound
#14, we performed a scratch wound assay. Results showed
that the increased concentration of compound #14 signifi-
cantly reduced SMC migration compared with untreated con-
trol SMCs (Figs. 4A, B).
Effects of the ECM Metalloproteinase Inducer
(EMMPRIN) and MMP Activation
RESULTS
To investigate the effect of compound #14 on the extra-
cellular MMP inducer, EMMPRIN, we performed western
blot analysis. The activation level of EMMPRIN was higher
in the collagen type I–treated group than in the control group.
It has been known that collagen type I acts as a signaling
molecule, which affects vascular SMC growth and migra-
tion.12 The activation level of EMMPRIN significantly
decreased in response to treatment with increased concen-
trations of compound #14 (Figs. 5A, B).
In Vitro Antiproliferative Effect on SMCs
Through fractionation process of Cordyceps extracts by
preparative high-pressure liquid chromatography, we identi-
fied some compounds from the peaks in the chromatogram.
Because mass producing these compounds was difficult, we
designed and synthesized their structural derivatives. Next,
we tested these compounds for antiatherosclerotic potential.
To examine the activity of MMPs, we performed RT-
PCR. Collagen type I treatment in SMCs increased the
activities of MMP-2 and MMP-9 (Figs. 5C, D). However,
treatment with compound #14 reduced the activities of
MMP-2 and MMP-9 in a dose-dependent manner (Figs. 5C,
D).
Effects of Cyclooxygenase (COX)-2 Activation
Generally, it has been reported that COX-2 expression
is related to the mitogen-activated protein kinase path-
way.13,14 Accordingly, we examined the mRNA expression
levels of COX-2 in SMCs treated with collagen type I.
Interestingly, treatment with more than 20 mM of compound
#14 inhibited the collagen type I-induced COX-2 expression
in a dose-dependent manner (Figs. 6A, B).
DISCUSSION
In this study, we first demonstrated the newly synthe-
sized 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate to be
FIGURE 2. Antiproliferative effects of compound #14 on
SMCs. SMCs (1 · 106 cells/mL) were treated with compound
#14 as evaluated by the CCK assay (**P , 0.01, n = 6 per
group).
a
potential
chemical
compound
that
exhibits
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J Cardiovasc Pharmacolꢁ Volume 76, Number 1, July 2020
Vascular Smooth Muscle Cell Proliferation
FIGURE 3. Effect of compound #14
on neointima formation in balloon-
injured rats. Femoral arteries were
excised at
3 weeks after balloon
injury. A total of 20 mM compound #
14 of the Cordyceps extract was
administered for 3 weeks after the
balloon injury. The sections were
stained with H&E, and neointima
formation
was
evaluated.
A,
Representative photographs of H&E
staining. B, Quantification of neointimal areas performed by ImagePro software (**P , 0.01, n = 3 per group).
FIGURE 4. Effect of compound #14
on SMC migration. Migration assays
were performed using scratch wound
closure analysis. A, Representative
photograph of SMC wound closure
after incubation with compound #14.
Bars = 200 mM. B, Quantification of
cell migration using migrated cell
numbers. Control, (C). **P , 0.01
versus untreated SMCs, n = 3 per
group.
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Han et al
J Cardiovasc Pharmacolꢁ Volume 76, Number 1, July 2020
FIGURE 5. The inhibitory effects of
compound #14 on the expression of
EMMPRIN and MMPs in SMCs. SMCs
were serum starved and treated with
various concentrations of compound
#14 for 2 hours before the exposure
with 10-mg/mL collagen type I for 3
hours. A, The expression level of
EMMPRIN protein was determined by
western blot. Control, C. B,
Quantification of protein expression
by western blot analysis. **P , 0.01,
n = 3 per group. C, Representative
photograph of the RT-PCR result.
Agarose gel was electrophoresed and
visualized by ethidium bromide
staining. D, Quantification of mRNA
expression by RT-PCR analysis. **P ,
0.01, n = 3 per group.
antiatherosclerotic activity. The important findings were as
follows: First, the synthesized compound inhibited the pro-
liferation and migration of aortic SMCs. Second, this
compound significantly reduced in vivo neointimal hyperpla-
sia. Third, this compound markedly inhibited the activation of
EMMPRIN, MMP-2, and MMP-9. These results suggest that
the newly synthesized compound can reduce restenosis by
regulating vessel wall remodeling in the intimal layer.
Generally, it has been known that atherosclerosis
caused by a neointimal lesion in the arterial lumen leads to
various vascular diseases, such as peripheral vascular disease,
myocardial infarction, and stroke. One of the important
factors responsible for the pathogenesis of atherosclerosis is
SMC. The abnormal proliferation of SMCs can contribute to
restenosis, which is characterized by a narrowed vessel, due
to neointimal thickening. In addition, thrombosis is a main
cause of early restenosis, whereas fibrocellular proliferation,
including SMCs and inflammatory cells, is the major cause of
late restenosis. Thus, we explored natural compounds as
antiatherosclerotic drugs to treat vascular disease.
as basigin or CD147, is a glycoprotein that is enriched on the
surface of tumor cells and stimulates production of several
matrix metalloproteinases by adjacent stromal cells.15 In fact,
neointimal SMCs within atherosclerotic lesions synthesize
novel ECM components and induce the activation of
matrix-degrading proteases that remodel the neointimal envi-
ronment. During atherosclerosis and restenosis, matrix-
degrading metalloproteinase (MMP) has been reported to be
associated with the induction of SMC migration and hyper-
plasia.16,17 MMPs, which degrade most of the ECM and base-
ment membranes, are the proteinases that affect the
proliferation and migration of SMCs.18,19 In a previous study,
the correlation between MMP activation and SMC migration
was demonstrated using a balloon-injured carotid artery rat
model.17 The expression level of each MMP (MMP-2, -3, -7,
-9, -12, and -13) in SMCs differs depending on the cellular
state and environment. MMP-2 is expressed in quiescent
SMCs, whereas the others are expressed in injured or athero-
sclerotic arteries.20,21 It has been reported that MMP-2 and
MMP-9 are involved in SMC migration, which contributes to
the intimal thickening of vascular lesions in vivo. In addition,
overexpression of MMP-9 in SMCs has been shown to induce
expansive remodeling in the carotid artery of an injured rat
because of the increase in SMC migration and the decrease in
ECM. EMMPRIN has also been known to play an important
role as the inducer or activator in MMP expression and cell
migration.22
We demonstrated that natural products derived from
Cordyceps showed antiproliferation activity of SMCs.7 We
identified and synthesized its specific chemical compounds.
The newly synthesized compound was shown to exhibit anti-
migrative and antiproliferative activity for SMCs. We specu-
lated that the compound damaged SMCs and affected the cell
death and migration function.
This compound also suppressed the enzyme activity of
MMPs and its inducer EMMPRIN. EMMPRIN, also known
COX comprises 2 isoforms, COX-1 and COX-2. The
induction of COX-2 is mediated by inflammation, and this
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ꢀ
J Cardiovasc Pharmacolꢁ Volume 76, Number 1, July 2020
Vascular Smooth Muscle Cell Proliferation
FIGURE 6. The inhibitory effects of compound
#14 on the expression of COX-2 in SMCs. SMCs
were serum starved, and the SMCs were treated
with various concentrations of compound #14 for
2 hours before the exposure of 10 mg/mL of col-
lagen type I for 3 hours. A, Representative pho-
tograph of the RT-PCR result. The agarose gel was
electrophoresed and visualized using ethidium
bromide staining. B, Quantification of mRNA
expression performed by RT-PCR analysis. **P ,
0.01, n = 3 per group.
10. Oh CM, Cho S, Jang JY, et al. Cardioprotective potential of an SGLT2
inhibitor against Doxorubicin-induced heart failure. Korean Circ J. 2019;
49:1183–1195.
11. Cho HJ, Lee N, Lee JY, et al. Role of host tissues for sustained humoral
effects after endothelial progenitor cell transplantation into the ischemic
heart. J Exp Med. 2007;204:3257–3269.
12. Zhang WD, Bai HZ, Sawa Y, et al. Association of smooth muscle cell
phenotypic modulation with extracellular matrix alterations during neo-
intima formation in rabbit vein grafts. J Vasc Surg. 1999;30:169–183.
13. Bornfeldt KE, Campbell JS, Koyama H, et al. The mitogen-activated
protein kinase pathway can mediate growth inhibition and proliferation
in smooth muscle cells. Dependence on the availability of downstream
targets. J Clin Invest. 1997;100:875–885.
14. Dean JL, Brook M, Clark AR, et al. p38 mitogen-activated protein kinase
regulates cyclooxygenase-2 mRNA stability and transcription in
lipopolysaccharide-treated human monocytes. J Biol Chem. 1999;274:
264–269.
15. Guo H, Li R, Zucker S, et al. EMMPRIN (CD147), an inducer of matrix
metalloproteinase synthesis, also binds interstitial collagenase to the
tumor cell surface. Cancer Res. 2000;60:888–891.
16. Southgate KM, Fisher M, Banning AP, et al. Upregulation of basement
membrane-degrading metalloproteinase secretion after balloon injury of
pig carotid arteries. Circ Res. 1996;79:1177–1187.
17. Bendeck MP, Zempo N, Clowes AW, et al. Smooth muscle cell migra-
tion and matrix metalloproteinase expression after arterial injury in the
rat. Circ Res. 1994;75:539–545.
18. Creemers EE, Cleutjens JP, Smits JF, et al. Matrix metalloproteinase
inhibition after myocardial infarction: a new approach to prevent heart
failure? Circ Res. 2001;89:201–210.
regulates cellular processes involved in vessel remodeling,
including MMPs and chemokines.23 COX-2 expression is
associated with SMC proliferation and mitogen-activated pro-
tein kinase and mediates proliferation of SMCs.24,25
Consistent with these findings, we observed that treatment
with collagen type I enhanced the expression levels of
COX-2, MMP-2, and MMP-9 in SMCs. However, the com-
pound treatment reduced the collagen type I-induced expres-
sion of COX-2. Thus, these results confirm that the newly
synthesized compound possesses anti-inflammatory or antia-
therosclerotic potential.
Therefore, in this study, we demonstrated that 4-
methoxyphenyl (E)-3-(furan-3-yl) acrylate regulates mole-
cules of neointimal SMCs involved in the remodeling of the
vessel wall and ECM. In conclusion, the newly synthesized 4-
methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alter-
native therapeutic option for treating atherosclerosis.
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