Meiling Wu

Nanjing Medical University, Nanjing, Jiangsu Sheng, China

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Publications (6)12.9 Total impact

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    ABSTRACT: Cardiac fibroblasts play an important role in myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix proteins. Estrogen has been reported to have a number of cardioprotective properties. However, it is unclear whether estrogen affects cardiac fibroblast differentiation. The purpose of the present study was to investigate the effect of estrogen on angiotensin II-induced cardiac fibroblast proliferation and differentiation. Cardiac fibroblasts were stimulated with angiotensin II (1 microM) in the presence or absence of 17beta-estradiol (100 nM). Pretreatment of cardiac fibroblasts with 17beta-estradiol significantly inhibited angiotensin II-induced cardiac fibroblast proliferation and differentiation (indicated by a reduction in alpha-smooth muscle actin (alpha-SMA) expression) by 25% and 20%. Pretreatment of 17beta-estradiol significantly reduced angiotensin II-increased levels of phospho-p38 mitogen-activated protein kinase (MAPK) by 40% and nuclear factor-kappaB (NF-kappaB) binding activity in cardiac fibroblasts by 55%. Our data suggests estrogen could have an anti-fibrotic effect through limiting cardiac fibroblast proliferation and differentiation, which are the critical steps in the pathogenesis of cardiac fibrosis.
    European journal of pharmacology 06/2009; 616(1-3):155-9. · 2.59 Impact Factor
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    ABSTRACT: Plasma fibrinogen has been defined as a risk factor of cardiovascular disease and may play a role in the development of cardiac hypertrophy. We have previously demonstrated that the Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response protein 88 (MyD88)-dependent nuclear factor-kappaB (NF-kappaB) pathway is involved in cardiac hypertrophy. The present study aimed to investigate whether fibrinogen will stimulate the hypertrophic response of cardiac myocytes and to examine the role of the TLR4/MyD88/NF-kappaB pathway in fibrinogen-induced cardiac hypertrophy. Cardiac hypertrophy was induced by transverse aortic banding for 5 weeks in Sprague-Dawley rats. The deposition of fibrinogen in the left ventricle, as determined by immunohistochemistry and immunoblotting, was increased. Aortic banding also significantly enhanced the association of TLR4 with MyD88 and increased NF-kappaB activity. In-vitro studies showed that fibrinogen induced a dose-dependent, hypertrophic response of neonatal cardiomyocytes. Fibrinogen stimulation significantly increased myocyte size, 3H-leucine incorporation and mRNA levels of atrial natriuretic peptide (ANP); fibrinogen challenge also significantly increased associations of TLR4 with MyD88 and NF-kappaB binding activity. Transient transfection of cardiomyocytes with a dominant-negative MyD88 plasmid significantly attenuated the fibrinogen-induced hypertrophic response of neonatal cardiac myocytes and blunted fibrinogen-increased activation of the TLR4/MyD88/NF-kappaB signaling pathway. Our results suggest that fibrinogen induces hypertrophic response of cardiomyocytes partially through a TLR4-mediated, MyD88-dependent NF-kappaB pathway.
    Journal of Hypertension 05/2009; 27(5):1084-93. · 4.22 Impact Factor
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    ABSTRACT: We examined the role of Tollip in the hypertrophic response of cardiomyocytes. C57BL/6 mice were subjected to transverse aortic constriction (TAC) for 2 weeks and age-matched sham surgical operated mice served as control. TAC significantly reduced the association of Tollip with IRAK-1 by 66.4 percent and increased NF-kappaB binding activity by 86.5 percent and the levels of phospho-p38 by 114.6 percent in the myocardium compared with sham control, respectively. In vitro experiments showed that IL-1beta stimulation also significantly reduced the association of Tollip with IRAK-1 and increased NF-kappaB binding activity in neonatal cardiomyocytes. Tollip overexpression by transfection of cardiac myocytes significantly attenuated the IL-1beta-induced hypertrophic response of cardiac myocytes as evidenced by reduced cell size (16.4 percent) and decreased ANP expression (33.3 percent). Overexpression of Tollip also reduced NF-kappaB binding activity by 30.7 percent and phospho-p38 by 47.1 percent, respectively. The results suggest that Tollip could be a negative regulator during the development of cardiac hypertrophy. The negative regulation of cardiac hypertrophy by Tollip may involve downregulation of the MyD88-dependent NF-kappaB activation pathway.
    Frontiers in Bioscience 02/2009; 14:2747-56. · 3.29 Impact Factor
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    ABSTRACT: This study was to examine the effect of estrogen on mechanical stretching-induced cardiac dysfunction in an isolated heart model. The isolated rat hearts were perfused via the Langendorff system and exposed to left ventricular stretching. One group hearts (n=6) were perfused with 17β-estradiol (100nM) and the other group hearts (n=6) were perfused with estrogen plus its receptor antagonist ICI182,780 (1μM) before myocardial stretching was performed. Control hearts (n=6) were perfused with perfusion buffer. Cardiac functions were recorded. At the end of perfusion, the hearts were harvested and the levels of tumor necrosis factor-alpha (TNF-alpha), phospho-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) binding activity were examined. Acute ventricular stretching resulted in significantly decrease in left ventricular developed pressure (LVDP) by 42.7%, maximal positive and negative values of the first derivative of pressure (+dP/dt and −dP/dt) by 43.2%, and 43.5%, respectively. The levels of TNF-alpha, phospho-p38 MAPK and NF-κB DNA binding activity were significantly increased following myocardial stretching. In 17β-estradiol treated hearts, the myocardial functions were significantly improved. The levels of TNF-alpha, phospho-p38 MAPK, and NF-κB binding activity in myocardium were also significantly reduced by 35.7%, 56.9%, and 50%, respectively, compared with untreated stretched hearts. The beneficial effects of 17β-estradiol on the stretched hearts were abolished by ICI182,780. The results suggest that pharmacological dose of 17β-estradiol will attenuate stretching-induced cardiac dysfunction in an isolated heart model. The mechanisms could involve in blunting p38 MAPK and NF-κB signaling.
    Steroids 08/2008; 73(7):720-726. · 2.80 Impact Factor
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    ABSTRACT: ObjectiveCarbamylated EPO(CEPO) is a derivative of erythropoietin(EPO) by subjecting it to carbamylation. It does not stimulate erythropoiesis, but effectively protects tissue from injury. The present study was to investigate the effect of CEPO treatment using in vitro models of hypoxia/reoxygenation(H/R).MethodsCardiomyocytes were exposed to hypoxia(95% N2 and 5% C02) for 1 hour followed by 4 hours of reoxygenation(95% 02 and 5% C02). CEPO was administered after hypoxia, just before reoxygenation. The apoptotic cardiomyocytes were determined by flow cytometry. The level of protein was assessed by western blot analysis.ResultsCEPO treatment significantly decreased the apoptotic cardiomyocytes by 54.20% compared with H/R group. Western blot analysis showed that CEPO administration increased the level of Bcl-2(an antiapoptotic protein) by 62.22% compared with H/R group.ConclusionAcute administration of CEPO protected cardiomyocytes from H/R-induced apoptosis. CEPO protected cardiomyocytes with a concomitant upregulation of Bcl-2 after H/R injury.
    Journal of Nanjing Medical University. 03/2008;
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    ABSTRACT: Objective Carbamylated EPO(CEPO) is a derivative of erythropoietin(EPO) by subjecting it to carbamylation. It does not stimulate erythropoiesis, but effectively protects tissue from injury. The present study was to investigate the effect of CEPO treatment using in vitro models of hypoxia/reoxygenation(H/R).
    Journal of Nanjing Medical University 01/2008; 22(2):71-74.