Yuedong Ma

Sun Yat-Sen University, Guangzhou, Guangdong Sheng, China

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Publications (8)22.92 Total impact

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    ABSTRACT: Although the role of the ubiquitin-proteasome system (UPS) in cardiac hypertrophy induced by pressure overload has been consistently studied, the fundamental importance of the UPS in cardiac fibrosis has received much less attention. Our previous study found that proteasome inhibitor (MG132) treatment attenuated cardiac fibrosis and heart failure during the early and middle stages of pressure overload. However, the effects of this inhibitor on late-stage pressure overload hearts remain unclear and controversial. The present study was designed to investigate the effects and possible mechanisms of MG132 on cardiac fibrosis and dysfunction during the late stages of pressure overload. Male Sprague Dawley rats with abdominal aortic constriction (AAC) or a sham operation received an intraperitoneal injection of MG132 (0.1 mgkg(-1)day(-1)) or vehicle for 16 weeks. Left ventricular (LV) function, collagen deposition and Ang II levels were evaluated at study termination. Ang II-stimulated adult rat cardiac fibroblasts were utilized to examine the effects of MG132 on collagen synthesis and the relationship between the renin-angiotensin- aldosterone system (RAAS) and the UPS. MG132 treatment attenuated ventricular dysfunction by suppressing cardiac fibrosis rather than inhibiting cardiac hypertrophy during the late-stages of pressure overload. We also found that Ang II activates UPS in the heart and MG132 attenuates Ang II-induced collagen synthesis via suppression of the NF-κB/TGF-β/Smad2 signaling pathways. Proteasome inhibition therefore could provide a new promising therapeutic strategy to prevent cardiac fibrosis and progression of heart failure even during the late-stages of pressure overload.
    Biochemical pharmacology 11/2012; · 4.25 Impact Factor
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    ABSTRACT: Objective: The purpose of the present study was to investigate the value of ox-LDL and oxidation ratio of LDL (ox-LDL/TC, ox-LDL/HDL-C and ox-LDL/LDL-C) in diagnosis and prognosis evaluation in CAD patients. Also, we aimed to observe the effect of statins on reducing level of ox-LDL and oxidation ratio of LDL, and explore whether statins still have similar effect on ox-LDL in a short period of therapy (within 2 weeks). Methods: Blood ox-LDL, TC, HDL-C, LDL-C, and TG were measured in cases with acute myocardial infarction (AMI, n=177), unstable angina pectoris (UAP, n=195), stable angina pectoris (SAP, n=228), normal control (n=120), and high risk control (n=140). Results: Mean value of ox-LDL and oxidation ratio of LDL was significantly higher in the CAD group than in the two control groups. The AUC of ROC curve of ox-LDL, ox-LDL/TC, ox-LDL/HDL-C, ox-LDL/LDL-C and apoA1/apoB were more than 0.50 (P < 0.001). Multivariate logistic regression analysis showed that age and ox-LDL/LDL-C related with short-term, while ox-LDL/LDL-C and ox-LDL/TC related with long-term prognosis (p < 0.05). Furthermore, after treatment with statins for 2 weeks, TC, LDL-C, ox-LDL, ox-LDL/TC, ox-LDL/HDL-C and ox-LDL/LDL-C decreased by 22%, 28%, 38%, 29%, 23% and 25% respectively. And the reduction of ox-LDL by statins is independent of lowering of LDL-C and TC. Conclusions: Ox-LDL and oxidation ratio of LDL are closely related with AS, and they are better biomarkers for discriminating between patients with coronary artery disease and healthy subjects. In addition, statins can decrease level of ox-LDL significantly, which is independent of lowering of LDL-C and TC.
    Disease markers 10/2012; · 2.14 Impact Factor
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    ABSTRACT: The recent studies indicated that the epithelial cell adhesion molecule E-cadherin is a well-recognized molecule that is important in cell adhesion. To further investigate the molecular basis of this notion, we used small-interfering RNA to inhibit E-cadherin function and found that loss of E-cadherin promoted Colorectal cancer cell growth, invasion and drug resistance through induction of β-catenin nuclear translocation and epithelial-to-mesenchymal transition. Further analysis of E-cadherin expression with clinicopathologic parameters showed that E-cadherin expression decreased in Colorectal cancer patients who developed liver metastasis (P = 0.043). These findings indicate that E-cadherin loss in tumors contributes to progression and metastatic dissemination. Thus, E-cadherin can act as a central modulator of the cell biological phenotypes and a potential prognostic marker in Colorectal cancer.
    Molecular Biology Reports 02/2012; 39(6):6707-14. · 2.51 Impact Factor
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    ABSTRACT: Although MG132, a proteasome inhibitor, is suggested to impede secondary cardiac remodeling after hypertension, the mechanism and optimal duration of treatment remain unknown. This study was designed to investigate the effects and possible mechanism of MG132 on hypertension-induced cardiac remodeling. Male Sprague-Dawley rats subjected to abdominal aortic constriction (AAC) or sham operation received an intraperitoneal injection of MG132 (0.1mgkg(-1)day(-1)) or vehicle over a 2- or 8-week period. In the end, left ventricular (LV) function was evaluated with echocardiography and pressure tracing. Collagen deposition within the LV myocardium was assessed with Masson's trichrome staining. Ubiquitin-proteasome system (UPS), NF-κB, I-κB, TGFβ1 and Smad2 within the LV tissue were evaluated. In addition, angiotensin II within both plasma and LV tissue was also examined. Compared with the sham groups, the vehicle-treated AAC group exhibited a higher angiotensin II level, LV/body weight ratio, septal and posterior wall thicknesses, and a markedly reduced cardiac function (P<0.05). Treatment with MG132 for 8 weeks attenuated these cardiac remodeling parameters and improved cardiac function (P<0.01). 2- and 8-week hypertension led to activation of UPS, which was followed by activation of NF-κB and increased expression of TGFβ1 and Smad2 (P<0.01). MG132 significantly inhibited NF-κB activity and down-regulate the levels of TGFβ1 and Smad2 expression by 2 and still at 8 weeks (P<0.01). Short- and long-term treatment with MG132 significantly attenuated hypertension-induced cardiac remodeling and dysfunction, which may be mediated by the NF-κB/TGFβ1 signaling pathway.
    Biochemical pharmacology 03/2011; 81(10):1228-36. · 4.25 Impact Factor
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    ABSTRACT: The nuclear factor (NF)-κB signaling pathway is an important intracellular mediator of cardiac hypertrophy. Recent studies have indicated that the anti-malarial agent artemisinin has the ability to inhibit NF-κB activation. We hypothesized that artemisinin would suppress cardiac hypertrophy by inhibiting NF-κB signal pathways. We tested this hypothesis using primary cultured rat cardiac myocytes and well-established rat models of cardiac hypertrophy. Artemisinin blocked angiotensin II-induced cardiac hypertrophy in vitro in a concentration-dependent manner. Furthermore, artemisinin protected against rat cardiac hypertrophy induced by transaortic constriction (TAC), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in cardiac nuclear extracts of banded rats that was prevented by artemisinin treatment. Banded rats treated with oral artemisinin, compared with untreated rats, showed significantly decreased the levels of IL-6, TNF-α and MCP-1 mRNA expression and increased protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. The effect of artemisinin on cardiac hypertrophy was blocked after IκB-α was silenced by transfection of cardiomyocytes with IκB-α siRNA. Our results indicate that artemisinin inhibits cardiomyocyte growth by interfering with NF-κB signaling.
    European journal of pharmacology 12/2010; 649(1-3):277-84. · 2.59 Impact Factor
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    ABSTRACT: Proteasome inhibitors are involved in cell cycle control, growth and inflammatory signaling, and transcriptional regulation of mitotic cells. A recent study has suggested that specific proteasome inhibitor MG132 may suppress cardiomyocyte hypertrophy in vitro. However, the underlying molecular mechanisms are not clear. In this study, we investigated the effects of long-term MG132 treatment on cardiac hypertrophy and the related molecular mechanisms in vivo. MG132 (0.1 mg/kg/day) was intraperitoneally injected to rats with abdominal aortic banding (AAB) for 8 weeks. Results showed that treatment with MG132 significantly attenuated left ventricular (LV) myocyte area, LV weight/body weight, and lung weight/body weight ratios, decreased LV diastolic diameter and wall thickness, and increased fractional shortening in AAB rats. AAB induced the phosphorylation of ERK1/2, JNK1, and p38 in cardiac myocytes. The elevated phosphorylation levels of ERK1/2 and JNK1 in AAB rats were significantly reversed by MG132 treatment. In conclusion, our results suggested that long-term treatment with MG132 attenuates pressureoverload-induced cardiac hypertrophy and improves cardiac function in AAB rats through regulation of ERK1/2 and JNK1 signaling pathways.
    Acta Biochimica et Biophysica Sinica 04/2010; 42(4):253-8. · 1.81 Impact Factor
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    ABSTRACT: Glioma is an extremely aggressive and lethal form of brain cancer. Despite recent advances in diagnostics and treatments, prognosis for advanced patients suffering from these diseases remains poor. Therefore, identification of new therapeutic targets for glioma is of significant importance. In this study, we identified the important role of Smad interacting protein 1 (SIP1; also known as ZEB2) in glioma. We firstly found that SIP1 expression was high in four tumorigenic glioma cell lines but low in two nontumorigenic glioma cell lines. By knockdown or overexpression assay, we discovered that knockdown of SIP1 expression statistically significantly inhibited cell migration and invasion of tumorigenic glioma cells, while overexpression of SIP1 promoted cell migration and invasion of nontumorigenic glioma cells. SIP1 knockdown inhibits and overexpression promotes glioma cell clonogenicity in vitro. Further studies identified that SIP1 overexpression inhibits expression of E-cadherin and enhances expression of mesenchymal proteins such as fibronectin and vimentin. This study supports the rationale for developing SIP1 as a potential therapeutic and diagnostic target for gliomas.
    Journal of Neuro-Oncology 10/2009; 97(2):225-32. · 3.12 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) is the third most common cancer in the world. Despite recent advances in diagnostics and treatment, prognosis for patients with advanced disease is still poor. microRNAs (miRNAs) are a class of endogenous, small noncoding RNA molecules which are crucial regulators of gene expression at the posttranscriptional level. miRNAs participate in many biological events and play an important role in various human diseases, including CRC. This study is to identify the role of miR-141 in migration and invasion of CRC cells. Expression of miR-141 and Smad interacting protein 1 (SIP1) were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. The effect of miR-141 on migration and invasion of CRC cells was investigated using wound healing assay and Matrigel invasion assay in vitro. The regulation effect of miR-141 on SIP1 was evaluated by dual-luciferase reporter assay. We demonstrated that miR-141 levels correlate inversely with SIP1 protein levels as well as cell migration and invasion of CRC cells. SIP1 was identified as a functional target of miR-141. miR-141 regulates SIP1 to inhibit migration and invasion of CRC cells. miR-141 and SIP1 might be candidate therapeutic targets in CRC.
    Digestive Diseases and Sciences 10/2009; 55(8):2365-72. · 2.26 Impact Factor

Publication Stats

98 Citations
22.92 Total Impact Points

Institutions

  • 2009–2012
    • Sun Yat-Sen University
      • Department of Cardiology
      Guangzhou, Guangdong Sheng, China
    • Sun Yat-Sen University of Medical Sciences
      • • Department of Pathology
      • • Department of Internal Medicine
      Shengcheng, Guangdong, China