Ya Miao

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai Shi, China

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Publications (14)17.36 Total impact

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    ABSTRACT: Angiotensin II (Ang II) and transforming growth factor β (TGFβ) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)-mediated TGFβ1/Smads signaling pathway specifically affects vascular fibrosis in diabetic rats and whether valsartan, an Ang II subtype 1 receptor blocker, has an anti-fibrotic effect. Age-matched male Wistar rats were randomly divided into 3 groups: control (n = 8), diabetes (n = 16) and valsartan (30 mg/kg/day) (n = 16). Type 2 diabetes mellitus (T2DM) was induced by a high-calorie diet and streptozotocin injection. Morphological and biomechanical properties of the thoracic aorta were assessed by echocardiography and cardiac catheterization. Masson staining was used for histological evaluation of extracellular matrix (ECM). The expression of components in the TSP1-mediated TGFβ1/Smads signaling pathway was analyzed by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. As compared with controls, diabetic aortas showed reduced distensibility and compliance, with excess ECM deposition. Components in the TSP1-mediated TGFβ1/Smads signaling pathway, including TSP1, TGFβ1, TGFβ type II receptor (TβRII), Smad2 and Smad3, were accumulated in vascular smooth muscle cytoplasm of diabetic aortas and their protein and mRNA levels were upregulated. All these abnormalities were attenuated by valsartan. TSP1-mediated TGFβ1/Smads pathway activation plays an important role in marcovascular remodeling in T2DM in rat. Valsartan can block the pathway and ameliorate vascular fibrosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1053842818141195.
    Diagnostic Pathology 04/2015; 10(1):18. DOI:10.1186/s13000-015-0246-8 · 2.41 Impact Factor
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    ABSTRACT: Accumulating evidences demonstrated that epigenetic modification of the expression of specific genes contributed to the pathogenesis of neurological disorders with dementia, including Alzheimer's disease (AD). Emerging reports also found the reduction of hippocampal brain-derived neurotrophic factor (BDNF) in the patients and rodent models of AD, while the mechanism and functional significance remain debated. The present study aims to study the epigenetic mechanism underlying the BDNF reduction and its functional significance in the rats with hippocampal infusion of amyloid fibrils. In the rats injected with amyloid fibrils, significant decreases of BDNF expression and the mRNA of Bdnf exon VI were found in the hippocampal CA1 area. Significantly increased hippocampal HDAC2 expression and its occupancy in the promoter region of Bdnf exon VI were also observed, thus contributing to the histone H3 deacetylation and BDNF suppression in the hippocampal CA1 in the rats injected with amyloid fibrils. Inhibition of HDAC2 activity by trichostatin A substantially recovered the histone H3 acetylation in the promoter region of Bdnf exon VI and BDNF expression, thus mitigating the synaptic dysfunction and memory deficiency induced by amyloid fibrils. These results elucidate the epigenetic mechanism underlying the BDNF reduction induced by amyloid fibrils, and provided novel insights into the pathogenic mechanism of Alzheimer's disease.
    Pharmacology Biochemistry and Behavior 09/2014; DOI:10.1016/j.pbb.2014.09.009 · 2.82 Impact Factor
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    ABSTRACT: To evaluate diastolic function alterations of the right ventricle (RV) by echocardiography in type 2 diabetic rat models. Male Wistar rats were divided into 2 groups: a control group (n = 8) and a diabetic group (n = 16, with 11 remaining at the end of the experiment), which was fed a high-fat and high-calorie diet and injected with streptozotocin (STZ). RV diastolic functional alteration of rat models was studied by the tricuspid flow Doppler (Ep, Ap, and Ep/Ap) and tissue Doppler imaging (TDI) (Em, Am, and Em/Am) of the lateral tricuspid annulus. RV structural alteration of rat models was studied by standard 2D and M-mode echocardiography. Compared with-the control group rats, at the 12th week after STZ injection, the rats of the diabetic group developed RV diastolic dysfunction, lower Em, and lower ratios (Ep/Ap, Em/Am). At the end of the experiment, at the 16th week after STZ injection, the rats of the diabetic group showed further decreased Ep, Em, and ratios (Ep/Ap, Em/Am) and significantly higher RV diameters compared with the control group rats. We demonstrated that the diastolic dysfunction of the RV was the earliest complication observed in type 2 diabetic rat models, using TDI and tricuspid flow Doppler. TDI showed a high sensitivity in detecting changes of RV diastolic function.
    Turkish Journal of Medical Sciences 01/2014; 44:448-453. DOI:10.3906/sag-1212-12 · 0.84 Impact Factor
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    ABSTRACT: To evaluate the protective effects of alprostadil on contrast-induced nephropathy (CIN) in elderly patients. We randomized 370 patients into the control or alprostadil group. The patients in the control group were injected with 100 ml sterile saline and the patients in the alprostadil group with alprostadil (0.4 μg/kg/day) in 100 ml sterile saline before and after iohexol-enhanced (100 ml) computed tomography (CT). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (CysC), and creatinine clearance (Ccr) were analyzed or calculated. ΔScr and ΔCysC were determined by the changes between baseline and highest Scr and CysC levels. The standard for CIN was a postdose Scr increase >44.2 μmol/l or >25 % over baseline. In the control group, peak Scr (P < 0.05) and ΔScr (P < 0.01) were higher than those in the alprostadil group. The postdose CysC at 24 h (P < 0.05), 48 h (P < 0.05), and 72 h (P < 0.05), peak CysC (P < 0.01), and ΔCysC (P < 0.05) in the control group were higher than those in the alprostadil group. The incidence of CIN in the control group was 22.2 %, which was higher than in the alprostadil group (9.1 %, P < 0.01). Subgroup analyses in patients with advanced age (≥80 years), concomitant hypertension or diabetes, and abnormal baseline renal function (Ccr ≤60 ml/min) showed that the alprostadil group had lower ΔScr and ΔCysC than the control group after contrast-enhanced CT examination in all four subgroups (P < 0.05 or P < 0.01). In this cohort of older patients undergoing contrast CT, the use of alprostadil reduced the incidence of CIN.
    International Urology and Nephrology 07/2013; 45(4). DOI:10.1007/s11255-013-0484-1 · 1.29 Impact Factor
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    ABSTRACT: BACKGROUND:: The aim of this study was to evaluate the effect of CYP2D6*10 and APOE polymorphisms on both steady-state plasma concentrations (Cp) and clinical response of donepezil in patients with mild-to-moderate Alzheimer's disease (AD). METHODS:: A total of 110 Chinese AD patients participated in this study. Patients were treated with 5 to 10 mg of donepezil daily for 6 months. The genotypes of CYP2D6*10 and APOE were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The steady-state Cp of donepezil was measured by high-performance liquid chromatography-tandem mass spectrometric assay method. The cognition of patients was evaluated at baseline and at 6-month follow-up by Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subscale. RESULTS:: At 6-month follow-up, 56 of 96 patients (58.3%) were evaluated as responders and 40 patients (41.7%) as nonresponders to donepezil treatment. A significantly higher frequency of patients with genotypes CYP2D6*1/*10 and *10/*10 were found in responders than in nonresponders (P < 0.05). Besides, patients with CYP2D6*1/*10 and *10/*10 genotypes had higher Cp of donepezil and improved cognition scores than those with CYP2D6*1/*1 genotype (P < 0.05). However, the frequency of APOE [Latin Small Letter Open E]4 carriers and noncarriers showed no difference between the 2 groups (P > 0.05). CONCLUSIONS:: AD patients with mutant allele (*10) in CYP2D6 gene may respond better to donepezil than those with wild allele (*1). We did not find the relationship between APOE [Latin Small Letter Open E]4 status and the efficacy of donepezil in our study.
    The American Journal of the Medical Sciences 09/2012; 345(3). DOI:10.1097/MAJ.0b013e318255a8f9 · 1.52 Impact Factor
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    ABSTRACT: To assess the relationship between carotid flow velocity and cognitive impairment in patients with mild-moderate (<50%) carotid artery disease. We studied 407 participants with available carotid ultrasound and cognitive measures. We related peak systolic velocity (PSV) and end diastolic velocity (EDV) of internal carotid artery (ICA) and common carotid artery (CCA) and intimal medial thickness (IMT) to Mini Mental State Examination (MMSE), Clock Draw Test (CDT), Activities of Daily Living Scale (ADL)and Montreal Cognitive Assessment (MoCA). EDV of CCA was significantly different in higher and lower MoCA (MMSE) groups. Multiple regression analysis demonstrated that lower EDV was significantly associated with lower MoCA (+0.459 per standard deviation (SD), p<0. 01 for the left; +0.539 per SD, p<0. 01 for the right) and CDT (odds ratio (OR) 0.093, p< 0.05 for the left; OR) 0.120, p<0. 01 for the right) scores. PSV of left CCA (-0.205 per SD, p<0.05) and IMT (+42.536 per SD, p< 0.001) were associated with ADL. PSV of right CCA was associated with MMSE (+0.081 per SD, p<0.001). No significant relationship between ICA flow velocity and cognitive performance was observed. Our preliminary data show that common carotid artery flow velocity was associated with cognitive performance.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 07/2012; 39(4):502-7. · 1.60 Impact Factor
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    ABSTRACT: Evidence suggests that type 2 diabetes (T2DM) is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. A total of 248 aged T2DM patients wore a continuous glucose monitoring system (CGMS) for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions (MAGE) and mean of daily difference (MODD). All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination (MMSE). The relationship between MAGE and MODD and performance on these cognitive tests was assessed. The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.
    Biomedical and Environmental Sciences 02/2012; 25(1):1-7. DOI:10.3967/0895-3988.2012.01.001 · 1.26 Impact Factor
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    ABSTRACT: Type 2 diabetes has been recently recognized as an important risk factor for cognitive decline of patients with Alzheimer's disease (AD). But the roles of hyperinsulinemia (HI) and insulin resistance (IR) in the development of AD are still controversial. This study was designed to evaluate whether HI or IR influenced the cognitive functions of older cohort. The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose (FBG) and fasting insulin (FINS) were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. In our study, there were 180 participants with HI and 148 without HI, and 192 with IR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model 1 adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.
    Biomedical and Environmental Sciences 02/2012; 25(1):8-14. DOI:10.3967/0895-3988.2012.01.002 · 1.26 Impact Factor
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    ABSTRACT: Intravascular ultrasound elastography (IVUSE) is a promising imaging technique for early investigation of vulnerable plaques. Compared to radiofrequency signal processing, digital B-mode analysis is simple and of higher portability. However, rare studies have been reported validating the latter technique in vivo. In this study, we developed an IVUSE computer software system involving semi-automatic border delineation and block-matching algorithm and validated the system in vivo. Seven minipigs were fed with atherogenic diet for 40 weeks. For each pig, the endothelium of one side of the renal arteries was denuded at the fifth week. With cross-correlation analysis, Lagrangian strain was calculated from two intravascular ultrasound images acquired in situ. Sixty regions of interests were selected from 35 elastograms matched well with the corresponding histological slices. Plaque types within these regions were classified as fibrous, fibro-fatty or fatty on Masson's trichrome and Oil-red O staining. Macrophage infiltration was also evaluated with immunohistology. Comparison between the mean strain value of the region of interest and the histological results revealed significant differences in strain values among different plaque types and non-diseased artery walls. The extent of macrophage infiltration was found to be correlated positively with strain values. For identification of fibro-fatty and fibrous plaques and macrophage infiltration, the system showed high sensitivity (93, 96 and 92%, respectively) and specificity (89, 76 and 66%, respectively), as revealed by receiver operating characteristic analysis. Our IVUSE system based on B-mode analysis is capable of characterizing fibrous and fibro-fatty plaques and macrophage intensity, thus holds potential for identifying vulnerable plaque.
    The international journal of cardiovascular imaging 01/2011; 27(1):39-49. DOI:10.1007/s10554-010-9659-3 · 2.32 Impact Factor
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    ABSTRACT: Vascular complications associated with diabetes are the major cause for the increased morbidity and mortality in diabetic patients. However, the progression of vascular complications in diabetes is not well understood. We aimed to investigate the biomechanical and biochemical changes associated with vascular dysfunction in diabetic rats. Male Wistar rats were randomly divided into two groups: normal control (n = 8) and fat-fed, streptozotocin-treated diabetic rats (n = 11). After 16 weeks, Peterson's modulus of elasticity (Ep) and cross-sectional distensibility (CD) were calculated and compared between the two groups. Aortas were harvested from rats for histopathological and electron-microscopic analysis. Collagenous fibers were scattered in the extracellular matrix and invaded the elastic lamina in the aortas of diabetic rats, suggesting a significant accumulation of collagen in diabetic vessels. Compared with normal rats, diabetic rats showed significantly reduced aortic distensibility (CD: 0.10 +/- 0.04 vs. 0.17 +/- 0.08 kPa(-1), p = 0.033) and an increased aortic stiffness index (Ep: 0.25 +/- 0.13 vs. 0.15 +/- 0.05 x 10(6) dyn/cm(2), p = 0.045). Ep was positively and CD negatively correlated with glucose and collagen in diabetic rats. In diabetic rats, elastic properties of the aorta are impaired, being closely related to hyperglycemia-induced vascular wall remodeling.
    Cardiology 06/2009; 114(2):107-13. DOI:10.1159/000219211 · 2.04 Impact Factor
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    ABSTRACT: To study the activation of transforming growth factor (TGF)-beta(1)/Smads signal pathway in diabetic cardiomyopathy (DCM) and effects of valsartan thereon. 40 male Wistar rats were randomly divided into 3 groups: DCM group (n = 16, fed with high-calorie fat diet for 4 weeks, injected intraperitoneally with streptozocin so as to establish DCM model, and then perfused into the stomach with normal saline once daily since the injection of STZ for 16 weeks), valsartan group (n = 16, perfused into the stomach with valsartan at the dose of 30 mg/kg once a day for 16 weeks after the establishment of DCM model), and control group (n = 8, fed with normal diet and perfused into the stomach with normal saline once daily for 16 weeks). At the end of the experiment, the contents of fast blood-glucose (FBG), fast insulin (FIN), serum cholesterol, and triglyceride were detected, and insulin sensitivity index (ISI) was calculated. Cardiac catheterization was performed to measure the hemodynamics indexes: left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), and maximal rise/fall velocity of ventricular pressure (+/- dp/dt(max)), and the left ventricular diastolic function (T) was calculated. Pieces of myocardium tissue were taken out to undergo ultrastructural histopathological examination by transmission electron microscopy. The content of collagen was quantified by Masson three-color staining. Real-time RT-PCR and Western-blotting were used to detect the mRNA expression and protein expression of TGFbeta(1), TGFbetaRII, Smad2, Smad3, and Smad7. By the end of experiment the levels of FBG, triglyceride, and cholesterol increased and the ISI decreased significantly in the DCM and valsartan groups (all P < 0.01). Compared with the valsartan and control groups the levels of LVEDP and T significantly increased, and the levels of LVSP and +/- dp/dt(max), significantly decreased (all P < 0.01); and the LVEDP of the valsartan group was significantly higher than that of the control group and the +/- dp/dt(max) of the valsartan group was significantly lower than that of the control group (P < 0.01). The volume of collagen in the myocardial tissue of the DCM group was 17% +/- 3%, significantly higher than that of the control group (11% +/- 3%, P < 0.01). The content of collagen in the myocardial tissue of the valsartan group was lower significantly than that of the DCM group. The levels of mRNA expression of TGFbeta(1), TGFbetaRII, Smad2, and Smad3 were 0.0126 +/- 0.0057, 0.0877 +/- 0.0272, 0.0884 +/- 0.0146, and 0.012 +/- 0.0048 respectively, all significantly higher than those of the control group (0.0054 +/- 0.0009, 0.0523 +/- 0.0218, 0.0413 +/- 0.0186, and 0.0064 +/- 0.0021 respectively, all P < 0.05 - 0.01). The ratios Smad2/Smad7 and Smad3/Smad7 of the DCM group were significantly higher than those of the control group (both P < 0.05). The protein levels of TGFbeta(1), P-Smad2, and P-Smad3 were 143 +/- 17, 212 +/- 43, and 151 +/- 32 respectively, all significantly higher than those of the control group (103 +/- 18, 107 +/- 21, and 89 +/- 17 respectively, P < 0.01). The P-Smad2/Smad7 and P-Smad3/Smad7 of the DCM group were significantly higher than those of the control group (both P < 0.05), The Smad2/Smad7 (or P-Smad2/Smads7) and Smad3/Smad7 (or P-Smad3/Smads7) of the valsartan group was significantly lower than those of the DCM group (both P < 0.05). Activation of TGFbeta(1)/Smads signal pathway and imbalance between Smad2, 3 and Sma7 may be one of the mechanisms of myocardial interstitial fibrosis in DCM. Valsartan can prevent myocardium from damage by blocking the signal pathway.
    Zhonghua yi xue za zhi 02/2007; 87(6):366-70.
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    ABSTRACT: To study the activation of transforming growth factor (TGF)-beta(1)/Smads signal pathway in diabetic cardiomyopathy (DCM) and effects of valsartan thereon. 40 male Wistar rats were randomly divided into 3 groups: DCM group (n = 16, fed with high-calorie fat diet for 4 weeks, injected intraperitoneally with streptozocin so as to establish DCM model, and then perfused into the stomach with normal saline once daily since the injection of STZ for 16 weeks), valsartan group (n = 16, perfused into the stomach with valsartan at the dose of 30 mg/kg once a day for 16 weeks after the establishment of DCM model), and control group (n = 8, fed with normal diet and perfused into the stomach with normal saline once daily for 16 weeks). At the end of the experiment, the contents of fast blood-glucose (FBG), fast insulin (FIN), serum cholesterol, and triglyceride were detected, and insulin sensitivity index (ISI) was calculated. Cardiac catheterization was performed to measure the hemodynamics indexes: left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), and maximal rise/fall velocity of ventricular pressure (+/- dp/dt(max)), and the left ventricular diastolic function (T) was calculated. Pieces of myocardium tissue were taken out to undergo ultrastructural histopathological examination by transmission electron microscopy. The content of collagen was quantified by Masson three-color staining. Real-time RT-PCR and Western-blotting were used to detect the mRNA expression and protein expression of TGFbeta(1), TGFbetaRII, Smad2, Smad3, and Smad7. By the end of experiment the levels of FBG, triglyceride, and cholesterol increased and the ISI decreased significantly in the DCM and valsartan groups (all P < 0.01). Compared with the valsartan and control groups the levels of LVEDP and T significantly increased, and the levels of LVSP and +/- dp/dt(max), significantly decreased (all P < 0.01); and the LVEDP of the valsartan group was significantly higher than that of the control group and the +/- dp/dt(max) of the valsartan group was significantly lower than that of the control group (P < 0.01). The volume of collagen in the myocardial tissue of the DCM group was 17% +/- 3%, significantly higher than that of the control group (11% +/- 3%, P < 0.01). The content of collagen in the myocardial tissue of the valsartan group was lower significantly than that of the DCM group. The levels of mRNA expression of TGFbeta(1), TGFbetaRII, Smad2, and Smad3 were 0.0126 +/- 0.0057, 0.0877 +/- 0.0272, 0.0884 +/- 0.0146, and 0.012 +/- 0.0048 respectively, all significantly higher than those of the control group (0.0054 +/- 0.0009, 0.0523 +/- 0.0218, 0.0413 +/- 0.0186, and 0.0064 +/- 0.0021 respectively, all P < 0.05 - 0.01). The ratios Smad2/Smad7 and Smad3/Smad7 of the DCM group were significantly higher than those of the control group (both P < 0.05). The protein levels of TGFbeta(1), P-Smad2, and P-Smad3 were 143 +/- 17, 212 +/- 43, and 151 +/- 32 respectively, all significantly higher than those of the control group (103 +/- 18, 107 +/- 21, and 89 +/- 17 respectively, P < 0.01). The P-Smad2/Smad7 and P-Smad3/Smad7 of the DCM group were significantly higher than those of the control group (both P < 0.05), The Smad2/Smad7 (or P-Smad2/Smads7) and Smad3/Smad7 (or P-Smad3/Smads7) of the valsartan group was significantly lower than those of the DCM group (both P < 0.05). Activation of TGFbeta(1)/Smads signal pathway and imbalance between Smad2, 3 and Sma7 may be one of the mechanisms of myocardial interstitial fibrosis in DCM. Valsartan can prevent myocardium from damage by blocking the signal pathway.
    Zhonghua yi xue za zhi 02/2007; 87(6):366-70.
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    ABSTRACT: Hyperglycemia could upregulate transforming growth factor-beta (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the rat in vivo and myocardial fibrosis was related to cardiac dysfunction in diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal pathways in the development of diabetic cardiomyopathy (DCM). Male Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30 mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or = 11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11). Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was monitored throughout the study. After hemodynamic measurements by the end of the study, myocardial collagen content was quantified in Masson-stained samples and the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were detected by Western blot. Compared with control group, cardiac function was decreased as shown by significantly reduced left ventricular systolic pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P < 0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also significantly higher than those of the control group. Moreover, myocardial collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were positively correlated to FBG and myocardial collagen (P < 0.05). However, there were no correlations between the protein expression of latent TGFbeta(1) and FBG and myocardial collagen. The pathway of glucose/TSP-1/TGFbeta(1) might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 03/2006; 34(3):217-21.
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    ABSTRACT: Tribbles, a protein family controlling mitogen-activated protein kinase cascades, might contribute to the remodeling process in dilated cardiomyopathy. We investigated the gene expression of Tribble 3 (TRB(3)), cardiac function and collagen changes in rats with diabetic cardiomyopathy (DCM) and the modulating effects of valsartan on them. Male Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30 mg/kg, i.p) was given at the 28th day, valsartan (30 mg.kg(-1).d(-1), n = 13) or placebo (n = 11) was administered at the 35th day to rats with fasting blood glucose > or = 11.1 mmol/L per gavage for another 12 weeks. Control rats (n = 8) were fed with regular chow. Fasting blood glucose was monitored throughout the study, left ventricular function was determined by echocardiography, myocardial collagen content quantified after Masson-staining and myocardial mRNA expression of TRB(3) detected by quantification real-time RT-PCR at the end of study. Cardiac function was significantly improved (EF: 74% +/- 10% vs. 66% +/- 7%, P < 0.05), myocardial collagen content decreased (13.23 +/- 3.14 vs. 16.92 +/- 3.18, P < 0.05) in rats with DCM treated with valsartan. Moreover, TRB(3) mRNA was significantly increased in rats with DCM compared to control rats (0.0198 +/- 0.0082 vs. 0.1108 +/- 0.0933, P < 0.05) and the increase could be significantly attenuated by valsartan (0.0367 +/- 0.0234, P < 0.05 vs. DCM). A significant positive correlation was observed between myocardial TRB(3) mRNA and myocardial collagen content (r = 0.67, P < 0.05) and between TRB(3) mRNA and fasting blood glucose (r = 0.69, P < 0.05) in rats with DCM. Our results show for the first time that myocardial TRB(3) mRNA is upregulated in rats with DCM and which could be down-regulated by valsartan.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 03/2006; 34(3):212-6.
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    ABSTRACT: To investigate the mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) by valsartan. Forty male wistar rats were randomly divided into 3 groups: DCM group, n = 16, fed with high-fat diet for 4 weeks and injected intraperitoneally with streptozocin (STZ) once to induce hyperglycemia so as to construct a DCM model, and then perfused into the stomach with normal saline; valsartan group, n = 16, to be constructed into DCM model and then perfused into the stomach with valsartan once daily; and control group (n = 8, fed with normal food and perfused into the stomach with normal saline. Four weeks after feeding (i.e., before injection of STZ), 1 week after STZ injection, and by the end of experiment after 12-hour fasting samples of venous blood were collected to detect the contents of triglyceride and fasting blood-glucose and insulin; by the end of experiment miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by Masson staining, real-time RT-PCR was used to detect the mRNA expression of thrombospondin (TSP)-1 and tumor growth factor (TGF)-beta(1) mRNA, expression, and Western blotting was used to detect the protein expression of TSP-1, active TGF-beta(1) (A-TGF-beta(1)) and latent TGF-beta(1) (L-TGF-beta(1)). By the end of the experiment, the body weights, and insulin sensitivity index were significantly lower and fasting blood-glucose, and serum triglyceride and cholesterol were significantly higher in the DCM group and valsartan group in comparison with those in the control group (all P < 0.01), however, there was no significant differences in fasting insulin among these 3 groups. The values of left ventricular systolic pressure (LVSP) and +/- dp/dt(max) were significantly lower and left ventricular end diastolic pressure were significantly higher in the DCM group in comparison with the control group (all P < 0.01). The LVSP and -dp/dt(max) were significantly higher and LVEDP was significantly lower in the valsartan group than in the DCM group (all P < 0.05). The LVEDP was significantly higher and -dp/dt(max) was significantly lower in the valsartan group than in the control group. Electron microscopy showed the distribution of a great amount of collagen in the myocardial interstitial tissue. The collagen content of the DCM group was 17 +/- 3, significantly higher than that of the control group (11 +/- 3, P < 0.05), and the collagen content of the valsartan group was 13 +/- 3, significantly lower than that of the DCM group (P < 0.05). The mRNA expression of TSP-1 and that of TGF-beta(1) were significant higher in the DCM group than in the control group (both P < 0.05), and were significantly lower in the valsartan group than in the DCM group (both P < 0.05); however, the TGF-beta(1) mRNA expression in the valsartan group was significantly higher in the valsartan group than in the control group (P < 0.05). The values of protein expression of TSP-1, A-TGF-beta(1) and L-TGF-beta(1) were all significantly higher in the DCM group than in the control group (all P < 0.05), and the values of protein expression of TSP-1 and A-TGF-beta(1) in the valsartan group were both significantly lower than those in the DCM group (both P < 0.05), however, there was no significant difference in the protein expression of L-TGF-beta(1) between the valsartan group and DCM group. Valsartan amelioorates myocardial interstitial fibrosis in DCM via TSP-1/TGF-beta(1) signaling pathway.
    Zhonghua yi xue za zhi 01/2006; 86(4):232-6.

Publication Stats

46 Citations
17.36 Total Impact Points

Institutions

  • 2012–2014
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2013
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
  • 2009
    • Shandong University
      • Key Laboratory for Cardiovascular Remodelling and Function Research
      Chi-nan-shih, Shandong Sheng, China