Yuh-Lien Chen

National Taiwan University, T’ai-pei, Taipei, Taiwan

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Publications (69)260.31 Total impact

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    ABSTRACT: Ischemia/reperfusion (I/R) injury to the kidney, a major cause of acute renal failure in humans, is associated with a high mortality, and the development of a new therapeutic strategy is therefore highly desirable. In this study, we examined the therapeutic potential of implantation of endothelial progenitor cells (EPCs) isolated from Wharton?s jelly of human umbilical cord in the treatment ofrenal I/R injury in mice. To visualize the localization of the transplanted EPCs, the cells were labeled with Q-tracker before injection into the renal capsule. Mice with renal I/R injury showed a significant increase in blood urea nitrogen and creatinine levels and these effects were decreased by EPC transplantation. The kidney injury score in the mice with I/R injury was also significantly decreased by EPC transplantation. EPC transplantation increased the microvascular density, and some of the EPCs surrounded, and were incorporated, into microvessels. In addition, EPC transplantation inhibited the I/R-induced cell apoptosis of endothelial, glomerular, and renal tubular cells, as demonstrated by TUNEL staining, and significantly reduced reactive oxygen species production and the expression of the inflammatory chemokines macrophage inflammatory protein-2 and keratinocyte-derivedcytokine, as shown by immunostaining and ELISA. Moreover, EPC transplantation reduced I/R-induced fibrosis, as demonstrated by immunostaining for S100A4, a fibroblast marker, and Jones silver staining. To our knowledge, this is first report that transplantation of EPCs from Wharton?s jelly of humanumbilical cords mightprovide a novel therapy for ischemic acute kidney injury by promoting angiogenesis and inhibiting apoptosis, inflammation, and fibrosis.
    Cell Transplantation 05/2014; · 4.42 Impact Factor
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    ABSTRACT: The expression of inflammatory cytokines on vascular walls is a critical event in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi) polysaccharides (EORPs), which is effective against immunological disorders, on interleukin- (IL-) 1 β expression by human aortic smooth muscle cells (HASMCs) and the underlying mechanism. The lipopolysaccharide- (LPS-) induced IL-1 β expression was significantly reduced when HASMCs were pretreated with EORP by Western blot and immunofluorescent staining. Pretreatment with 10 μ g/mL EORP decreased LPS-induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1 β expression with LPS treatment was only inhibited by pretreatment with the ERK1/2 inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP reduced the phosphorylation and nuclear translocation of nuclear factor- (NF-) κ B p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1 β expression was strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of EORP decreased IL-1 β expression. The level of IL-1 β expression in LPS-treated or in LPS/EORP-treated group was very low and was similar to that of the saline-treated group in toll-like receptor 4-deficient (TLR4(-/-)) mice. These findings suggest that EORP has the anti-inflammatory property and could prove useful in the prevention of vascular diseases and inflammatory responses.
    Evidence-based Complementary and Alternative Medicine 01/2014; 2014:305149. · 1.72 Impact Factor
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    ABSTRACT: Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-α induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-α-treated HAECs. The decrease in VCAM-1 expression in response to TNF-α treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-κB activation and the translocation of HuR (an RNA binding protein) in TNF-α-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-α-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-α-induced JNK/p38 phosphorylation, HuR translocation, NF-κB activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses.
    The American Journal of Chinese Medicine 01/2014; 42(3):619-37. · 2.28 Impact Factor
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    ABSTRACT: Accumulating evidence indicates that the regimen to increase adiponectin will provide a novel therapeutic strategy for inflammation and cardiovascular disorders. Here, we tested the effect of troglitazone (TG) and its newly synthesized derivative, 5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl-methoxy)-benzylidene]-2,4-thiazolidinedione (Δ2troglitazone, (Δ2TG)), on the adiponectin expression in monocytes/macrophages and the relative mechanisms. The expression of adiponectin was located in macrophages of atherosclerotic lesions from patients and cholesterol-fed rabbits. TG and Δ2TG enhanced adiponectin mRNA and protein expression in THP-1 cells by quantitative real-time PCR, Western blot, and immunocytochemistry. TG induced adiponectin mRNA expression through a PPARγ-dependent pathway whereas Δ2TG enhanced adiponectin mRNA expression through a PPARγ-independent pathway in THP-1 cells. Both TG and Δ2TG enhanced adiponectin mRNA expression through AMP-activated protein kinase (AMPK) activation. TG and Δ2TG decreased the adhesion of THP-1 cells to TNF-α-treated HUVECs and the inhibitory effect was abolished by specific antiadiponectin antibodies. TG- and Δ2TG-induced suppression on monocyte adhesion were inhibited by a selective AMPK inhibitor compound C. Our data suggest that the inhibitory effect of TG and Δ2TG on monocyte adhesion might be at least in part through de novo adiponectin expression and activation of an AMPK-dependent pathway, which might play an important role in anti-inflammation and antiatherosclerosis.
    Mediators of Inflammation 01/2014; 2014:726068. · 3.88 Impact Factor
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    ABSTRACT: Keloids are characterized by the vigorously continuous production of extracellular matrix protein and aberrant cytokine activity in the dermis. There is a growing body of evidence that thalidomide, α-N-phthalimidoglutarimide, has anti-fibrotic properties. The aims were to examine possible therapeutic effects of thalidomide on fibronectin expression in transforming growth factor-β1 (TGF-β1)-treated normal fibroblasts (NFs) and keloid-derived fibroblasts (KFs) and the underlying mechanism of action, especially the involvement of mitogen-activated protein kinase (MAPKs) and Sma- and Mad-related family (Smads) pathways. In surgically removed human tissues, TGF-β1 and fibronectin immunoreactivity was high in keloid tissue, but barely detectable in normal tissue. TGF-β1 induced significant fibronectin expression in NFs and KFs and the effect was inhibited by pretreatment with thalidomide. TGF-β1 also induced phosphorylation of MAPKs (ERK1/2, p38, and JNK) and Smad2/3 and pretreatment with PD98059 (an ERK1/2 inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor) inhibited TGF-β1-induced fibronectin expression. Furthermore, pretreatment with thalidomide inhibited the TGF-β1-induced phosphorylation of p38 and Smad3, but not that of ERK1/2, JNK, and Smad2. In addition, thalidomide pretreatment inhibited the TGF-β-induced DNA binding activity of AP-1 and Smad3/4, caused fibronectin degradation by increasing the activity of matrix metalloproteinase 9, and decreased production of TGF-β1 and fibronectin and the number of fibroblasts in an in vivo keloid model. These results show that thalidomide has an antifibrotic effect on keloid fibroblasts that is caused by suppression of TGF-β1-induced p38 and Smad3 signaling. Our findings indicate that thalidomide may be a potential candidate drug for the treatment and prevention of keloids.
    Biochemical pharmacology 03/2013; · 4.25 Impact Factor
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    ABSTRACT: Renal ischemia rapidly mobilizes endothelial progenitor cells (EPCs), which provides renoprotection in acute kidney injury (AKI). Indoxyl sulfate (IS) is a protein-binding uremic toxin with a potential role in endothelial injury. In this study, we examined the effects and mechanisms of action of IS on EPCs in AKI. Forty-one consecutive patients (26 male; age, 70.1 ± 14.1 years) diagnosed with AKI according to the AKIN criteria were enrolled. The AKI patients had higher serum IS levels than patients with normal kidney function (1.35 ± 0.94 × 10(-4)M vs. 0.02 ± 0.02 × 10(-4)M, P < 0.01). IS levels were negatively correlated to the number of double-labeled (CD34(+)KDR(+)) circulating EPCs (P < 0.001). After IS stimulation, the cells displayed decreased expression of phosphorylated endothelial nitric oxide (NO) synthase, vascular cell adhesion molecule-1, increased reactive oxygen species, decreased proliferative capacity, increased senescence and autophagy, as well as decreased migration and angiogenesis. These effects of IS on EPCs were reversed by atorvastatin. Further, exogenous administration of IS significantly reduced EPC number in Tie2-GFP transgenic mice and attenuated NO signaling in aortic and kidney arteriolar endothelium after kidney ischemia-reperfusion injury in mice, and these effects were restored by atorvastatin. Our results are the first to demonstrate that circulating IS is elevated in AKI and has direct effects on EPCs via NO-dependent mechanisms both in vitro and in vivo. Targeting the IS-mediated pathways by NO-releasing statins such as atorvastatin may preempt disordered vascular wall pathology, and represent a novel EPC-rescued approach to impaired neovascularization after AKI.
    Angiogenesis 02/2013; · 4.41 Impact Factor
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    ABSTRACT: Endothelial progenitor cells (EPCs) move towards injured endothelium or inflamed tissues and incorporate into foci of neovascularisation, thereby improving blood flow and tissue repair. Patients with cardiovascular diseases have been shown to exhibit reduced EPC number and function. It has become increasingly apparent that these changes may be effected in response to enhanced oxidative stress, possibly as a result of systemic and localised inflammatory responses. The interplay between inflammation and oxidative stress affects the initiation, progression, and complications of cardiovascular diseases. Recent studies suggest that inflammation and oxidative stress modulate EPC bioactivity. Clinical medications with anti-inflammatory and antioxidant properties, such as statins, thiazolidinediones, angiotensin II receptor 1 blockers, and angiotensin-converting enzyme inhibitors, are currently administered to patients with cardiovascular diseases. These medications appear to exert beneficial effects on EPC biology. This review focuses on EPC biology and explores the links between oxidative stress, inflammation, and development of cardiovascular diseases.
    BioMed research international. 01/2013; 2013:845037.
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    ABSTRACT: Peripheral arterial diseases, the major complication of diabetes, can result in lower limb amputation. As endothelial progenitor cells (EPCs) are involved in neovascularization, the study was to examine whether EPCs isolated from Wharton's jelly (WJ-EPCs) of the umbilical cord, a rich source of mesenchymal stem cells, could reduce ischemia-induced hind limb injury in diabetic mice. We evaluated the effects of WJ-EPC transplantation on hind limb injury caused by femoral artery ligation in mice with streptozotocin (STZ)-induced diabetes. We found that the ischemic hind limb in mice with streptozotocin-induced diabetes showed decreased blood flow and capillary density and increased cell apoptosis and that these effects were significantly inhibited by injection of WJ-EPCs. In addition, HIF-1α and IL-8 were highly expressed in transplanted WJ-EPCs in the ischemic skeletal tissues and were present at high levels in hypoxia-treated cultured WJ-EPCs. Moreover, incubation of the NOR skeletal muscle cell line under hypoxic conditions in conditioned medium from EPCs cultured for 16 h under hypoxic conditions resulted in decreased expression of pro-apoptotic proteins and increased expression of anti-apoptotic proteins. The inhibition of HIF-1α or IL-8 expression by EPCs using HIF-1α siRNA or IL-8 siRNA, respectively, prevented this change in expression of apoptotic-related proteins. Wharton's jelly in the umbilical cord is a valuable source of EPCs and transplantation of these EPCs represents an innovative therapeutic strategy for treating diabetic ischemic tissues. The HIF-1α/IL-8 signalling pathway plays a critical role in the protective effects of EPCs in the ischemic hind limb of diabetic mice.
    Stem cells and development 12/2012; · 4.15 Impact Factor
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    ABSTRACT: Chronic elevation of glucose level activates vascular inflammation and increases endothelial adhesiveness to monocytes, an early sign of atherogenesis. This study aimed to elucidate the detailed mechanisms of high-glucose-induced endothelial inflammation, and to investigate the potential effects of Ginkgo biloba extract (GBE), an antioxidant herbal medicine, on such inflammation. Human aortic endothelial cells were cultured in high glucose or mannitol as osmotic control for 4 days. The expression of cytokines and adhesion molecules and the adhesiveness of endothelial cells to monocytes were examined. The effects of pretreatment of GBE or N-acetylcysteine, an antioxidant, were also investigated. Either high glucose or mannitol significantly increased reactive oxygen species (ROS) production, interleukin-6 secretion, intercellular adhesion molecule-1 (ICAM-1) expression, as well as endothelial adhesiveness to monocytes. The high-glucose-induced endothelial adhesiveness was significantly reduced either by an anti-ICAM-1 antibody or by an interleukin-6 neutralizing antibody. Interleukin-6 (5 ng/ml) significantly increased endothelial ICAM-1 expression. Piceatannol, a signal transducer and activator of transcription (STAT) 1/3 inhibitor, but not fludarabine, a STAT1 inhibitor, suppressed high-glucose-induced ICAM-1 expression. Pretreatment with GBE or N-acetylcysteine inhibited high-glucose-induced ROS, interleukin-6 production, STAT1/3 activation, ICAM-1 expression, and endothelial adhesiveness to monocytes. Long-term presence of high glucose induced STAT3 mediated ICAM-1 dependent endothelial adhesiveness to monocytes via the osmotic-related redox-dependent interleukin-6 pathways. GBE reduced high-glucose-induced endothelial inflammation mainly by inhibiting interleukin-6 activation. Future study is indicated to validate the antioxidant/anti-inflammatory strategy targeting on interleukin-6 for endothelial protection in in vivo and clinical hyperglycemia.
    Cardiovascular Diabetology 05/2012; 11:49. · 4.21 Impact Factor
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    ABSTRACT: Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress, but the mechanism of force-specific activation of their signaling to modulate cellular function remains unclear. We have demonstrated that bone morphogenetic protein receptor (BMPR)-specific Smad1/5 can be force-specifically activated by oscillatory shear stress (OSS) in ECs to cause cell cycle progression. Smad1/5 is highly activated in ECs of atherosclerotic lesions in diseased human coronary arteries from patients with end-stage heart failure undergoing heart transplantation and from apolipoprotein E-deficient mice. Application of OSS (0.5 ± 4 dyn/cm(2)) causes the sustained activation of Smad1/5 in ECs through activations of mammalian target of rapamycin and p70S6 kinase, leading to up-regulation of cyclin A and down-regulations of p21(CIP1) and p27(KIP1) and, hence, EC cycle progression. En face examination of rat aortas reveals high levels of phospho-Smad1/5 in ECs of the straight segment of thoracic aorta and the inner, but not the outer, curvature of aortic arch. Immunohistochemical and en face examinations of the experimentally stenosed abdominal aorta in rats show high levels of phospho-Smad1/5 in ECs at poststenotic sites, where OSS occurs. These OSS activations of EC Smad1/5 in vitro and in vivo are not inhibited by the BMP-specific antagonist Noggin and, hence, are independent of BMP ligand. Transfecting ECs with Smad1/5-specific small interfering RNAs inhibits the OSS-induced EC cycle progression. Our findings demonstrate the force-specificity of the activation of Smad1/5 and its contribution to cell cycle progression in ECs induced by disturbed flow.
    Proceedings of the National Academy of Sciences 05/2012; 109(20):7770-5. · 9.81 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) produced by cytokines induce the expression of inflammatory mediators in rheumatoid arthritis (RA). Heme oxygenase 1 (HO-1) exerts an antiinflammatory effect. The aim of this study was to examine the mechanisms underlying interleukin-1β (IL-1β)-induced cytosolic phospholipase A2 (cPLA2) expression through ROS generation as modulated by HO-1 in RA synovial fibroblasts (RASFs). IL-1β-induced ROS generation was determined by flow cytometry. The involvement of MAPKs and NADPH oxidase (NOX)/ROS in IL-1β-induced cPLA2 expression was investigated using pharmacologic inhibitors and transfection with small interfering RNAs (siRNAs) and was analyzed by Western blotting and promoter assay. Overexpression of HO-1 was performed by transfection of RASFs with a recombinant adenovirus containing human HO-1 plasmid. SCID mice with inflammation caused by IL-1β were infected with adenovirus containing HO-1. Histologic characterization of joint inflammation and local expression of cPLA2 were evaluated after treatment. IL-1β-induced cPLA2 expression was mediated through NOX activation/ROS production, which was attenuated by N-acetylcysteine (NAC; a scavenger of ROS), the inhibitors of NOX (diphenyleneiodonium chloride and apocynin), MEK-1/2 (U0126), and JNK-1/2 (SP600125), transfection with the respective siRNAs, and the overexpression of HO-1 in RASFs. IL-1β-induced cPLA2 expression was mediated through recruitment of activator protein 1 (AP-1) to the cPLA2 promoter region, which was attenuated by NAC and overexpression of HO-1. Furthermore, HO-1 overexpression inhibited IL-1β-mediated cPLA2 expression in SCID mice. In RASFs, IL-1β induced cPLA2 expression via activation of p42/p44 MAPK and JNK-1/2, leading to p47phox phosphorylation, ROS production, and AP-1 activation. The induction of HO-1 exerted protective effects on the pathogenesis of RA.
    Arthritis & Rheumatology 01/2012; 64(7):2114-25. · 7.48 Impact Factor
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    ABSTRACT: Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.
    BioMed Research International 01/2012; 2012:871272. · 2.71 Impact Factor
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    ABSTRACT: Magnetic nanoparticles (MNPs) of Fe(3)O(4) have been widely applied in many medical fields, but few studies have clearly shown the outcome of particles following intravenous injection. We performed a magnetic examination using scanning SQUID biosusceptometry (SSB). Based on the results of SSB analysis and those of established in vitro nonmagnetic bioassays, this study proposes a model of MNP metabolism consisting of an acute metabolic phase with an 8 h duration that is followed by a chronic metabolic phase that continues for 28 d following MNP injection. The major features included the delivery of the MNPs to the heart and other organs, the biodegradation of the MNPs in organs rich with macrophages, the excretion of iron metabolites in the urine, and the recovery of the iron load from the liver and the spleen. Increases in serum iron levels following MNP injection were accompanied by increases in the level of transferrin in the serum and the number of circulating red blood cells. Correlations between the in vivo and in vitro test results indicate the feasibility of using SSB examination for the measurement of MNP concentrations, implying future clinical applications of SSB for monitoring the hematological effects of MNP injection.
    PLoS ONE 01/2012; 7(11):e48510. · 3.53 Impact Factor
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    ABSTRACT: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor. The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections. VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*(2) signal and T(2) relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice. These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.
    International Journal of Nanomedicine 01/2012; 7:2833-42. · 4.20 Impact Factor
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    ABSTRACT: Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.
    Evidence-based Complementary and Alternative Medicine 01/2012; 2012:683872. · 1.72 Impact Factor
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    ABSTRACT: IntroductionChinese herbs are widely used as important remedies in Oriental integrative medicine. Magnolol is a small polyphenolic molecule with low toxicity that is isolated from the herb genus Magnolia. In preclinical experiments, magnolol was found to have anti-oxidative, anti-inflammatory, anti-tumorigenic, anti-diabetic, anti-microbial, anti-neurodegenerative and anti-depressant properties. Magnolol can also effectively regulate pain control, hormonal signalling, gastrointestinal and uterus modulation as well as provide cardiovascular and liver protective effects.
    European Journal of Integrative Medicine 12/2011; · 0.56 Impact Factor
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    ABSTRACT: Our previous study demonstrated that pigment epithelium-derived factor (PEDF) plays an important role in the proliferation and migration of human aortic smooth muscle cells (HASMCs). In the present study, we examined whether PEDF inhibited platelet-derived growth factor (PDGF)-stimulated HASMC migration and proliferation. PEDF dose-dependently reduced PDGF-induced HASMC migration and proliferation in vitro and also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21(Cip1) and increased expression of the cyclin-dependent kinase inhibitor p27(Kip1). The antiproliferative and antimigratory effects of PEDF were partially blocked by the PPARγ antagonist GW9662, but not by the PPARα antagonist MK886. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice injected intravenously with PEDF or vehicle. After 2 weeks, both the neointima/media area ratio and cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima were significantly reduced and again these effects were partially reversed by GW9662 pretreatment. Our data show that PEDF increases PPARγ activation, preventing entry of HASMCs into the cell cycle in vitro and reducing the neointimal area and cell proliferation in the neointima in vivo. Thus, PEDF may represent a safe and effective novel target for the prevention and treatment of vascular proliferative diseases.
    The international journal of biochemistry & cell biology 11/2011; 44(2):280-9. · 4.89 Impact Factor
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    ABSTRACT: Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21(Cip1) and upregulation of the cyclin-dependent kinase inhibitor p27(Kip1). The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100 mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67 ± 0.03 vs. 1.46 ± 0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases.
    Journal of Cellular Physiology 10/2011; 227(8):3063-71. · 4.22 Impact Factor
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    ABSTRACT: Primary aldosteronism (PA) is associated with a higher incidence of cardiovascular events, probably through mineralocorticoid receptor (MR)-dependent endothelial cell dysfunction, in comparison with essential hypertension (EH). Our objective was to investigate the number and function of endothelial progenitor cells (EPC) in PA and the relationship with arterial stiffness and disease progression. We conducted a prospective study of the change of EPC number and outcome of PA patients after treatment at a tertiary medical center. PRIMARY OUTCOMES: Changes in arterial stiffness and EPC number after treatment and the curability of hypertension were assessed. A total of 113 PA patients (87 patients diagnosed with aldosterone-producing adenoma, 26 with idiopathic hyperaldosteronism) and 55 patients with EH participated. PA patients had higher arterial stiffness than EH patients (P = 0.006), with a lower numbers of circulating EPC and endothelial colony-forming units (P < 0.05). The differences were ameliorated at 6 months after unilateral adrenalectomy or treatment with spironolactone. Expression of MR was identified in the EPC. The number of circulating EPC was inversely correlated with the plasma aldosterone concentration (P = 0.021), arterial stiffness (P = 0.029) and serum high-sensitivity C-reactive protein (P = 0.03). High-dose aldosterone (10(-5) and 10(-6) m) attenuated EPC proliferation and angiogenesis in vitro. Among the 45 patients who underwent unilateral adrenalectomy, 32 (71%) were cured of hypertension. The preoperative number of EPC [log(EPC number percent) >-3.6] predicted the curability of hypertension after adrenalectomy (P = 0.003). The relative deficiency of EPC in PA patients may contribute to aldosterone vasculopathy, which can be reversed by adrenalectomy and spironolactone. High aldosterone levels attenuated EPC proliferation and angiogenesis. Circulating EPC number may be a valuable biomarker to identify PA patients with a high incidence of arterial stiffness and to predict postoperative residual hypertension of aldosterone-producing adenoma.
    The Journal of Clinical Endocrinology and Metabolism 08/2011; 96(10):3175-83. · 6.31 Impact Factor
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    ABSTRACT: Viscolin, a major active component in a chloroform extract of Viscum coloratum, has antioxidative and anti-inflammatory properties. We focused on its effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α)-treated human umbilical vein endothelial cells (HUVECs). The TNF-α-induced expression of VCAM-1 was significantly reduced by respectively 38±7 or 34±16% when HUVECs were pretreated with 10 or 30μM viscolin, as shown by Western blotting, and was also significantly reduced by pretreatment with the antioxidants N-acetylcysteine, diphenylene iodonium chloride, and apocynin. Viscolin also reduced TNF-α-induced VCAM-1 mRNA expression and promoter activity, decreased reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and significantly reduced the binding of monocytes to TNF-α-stimulated HUVECs. The attenuation of TNF-α-induced VCAM-1 expression and cell adhesion was partly mediated by a decrease in JNK phosphorylation. Furthermore, viscolin reduced VCAM-1 expression in the aorta of TNF-α-treated mice in vivo. Taken together, these data show that viscolin inhibits TNF-α-induced JNK phosphorylation, nuclear translocation of NF-κB p65, and ROS generation and thereby suppresses VCAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that viscolin may prevent the development of atherosclerosis and inflammatory responses.
    Free Radical Biology and Medicine 07/2011; 51(7):1337-46. · 5.27 Impact Factor

Publication Stats

1k Citations
260.31 Total Impact Points

Institutions

  • 2005–2014
    • National Taiwan University
      • • College of Medicine
      • • Graduate Institute of Anatomy and Cell Biology
      • • School of Medicine
      T’ai-pei, Taipei, Taiwan
  • 2012
    • Chung Shan Medical University
      臺中市, Taiwan, Taiwan
  • 2008–2012
    • Chang Gung University
      • College of Medicine
      Taoyuan, Taiwan, Taiwan
  • 2001–2012
    • National Yang Ming University
      • • Department and Institute of Pharmacology
      • • Department of Biotechnology and Laboratory Science in Medicine
      • • Institute of Clinical Medicine
      • • Institute of Anatomy and Cell Biology
      Taipei, Taipei, Taiwan
  • 2011
    • National Central University
      • Department of Life Science
      Taoyuan City, Taiwan, Taiwan
  • 2010
    • China Medical University Hospital
      • Department of Radiology
      臺中市, Taiwan, Taiwan
    • National Taiwan Normal University
      • Department of Human Development & Family Studies
      Taipei, Taipei, Taiwan
  • 2009–2010
    • Kaohsiung Medical University
      • Department of Respiratory Therapy
      Kao-hsiung-shih, Kaohsiung, Taiwan
    • National Taiwan University Hospital
      • Department of Internal Medicine
      T’ai-pei, Taipei, Taiwan
  • 2007
    • National Defense Medical Center
      • Graduate Institute of Medical Sciences
      Taipei, Taipei, Taiwan
    • Tri-Service General Hospital
      T’ai-pei, Taipei, Taiwan
  • 2001–2007
    • Taipei Veterans General Hospital
      • Cardiology Division
      T’ai-pei, Taipei, Taiwan