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ABSTRACT: Endothelial activation characterized by the expression of multiple chemokines and adhesive molecules is a critical initial step of vascular inflammation which results in recruitment of leukocytes into sub-endothelial layer of vascular wall and triggers vascular inflammatory diseases such as atherosclerosis. Although inhibiting the endothelial inflammation has already been well recognized as a therapeutic strategy in vascular inflammatory diseases, the therapeutic targets are still elusive. In the present study we found that Zc3h12c, a recently discovered CCCH-zinc finger containing protein, significantly inhibited endothelial cell inflammatory response in vitro. Overexpression of Zc3h12c significantly attenuated tumor necrosis factor a (TNFa) induced expression of chemokines and adhesive molecules, and thus reduced monocyte adherence to human umbilical vein endothelial cells (HUVECs). Conversely, siRNA-mediated knocking down of Zc3h12c increased TNFα-induced expression of chemokines and adhesive molecules in HUVECs. Furthermore, forced expression of Zc3h12c decreased TNFα-induced IKKa/b and IkBa phosphorylation and p65 nuclear translocation, suggesting that Zc3h12c exerted the anti-inflammatory function probably by suppressing nuclear factor-kB (NF-kB) pathway. Thus, Zc3h12c is an endogenous inhibitor of TNFα-induced inflammatory signaling in HUVECs and might be a therapeutic target in vascular inflammatory diseases.
Biochemical Journal 01/2013; · 4.90 Impact Factor
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ABSTRACT: Proliferation of vascular smooth muscle cells (VSMCs) in response to vascular injury plays a critical role in vascular lesion formation. Emerging data suggest that peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) is a key regulator of energy metabolism and other biological processes. However, the physiological role of PGC-1β in VSMCs remains unknown. A decrease in PGC-1β expression was observed in the balloon injured carotid arteries in rat. PGC-1β overexpression substantially inhibited neointima formation in vivo and markedly inhibited VSMC proliferation and induced cell cycle arrest at G1/S transition in vitro. Accordingly, overexpression of PGC-1β decreased the expression of mini chromosome maintenance 4 (MCM4), which leads to a decreased loading of MCM complex to chromatin at replication origins and decreased cyclin D1 level, whereas PGC-1β loss-of-function by adenovirus containing PGC-1β shRNA resulted in the opposite effect. Transcription factor AP-1 was involved in the downregulation of MCM4 expression. Furthermore, PGC-1β is upregulated by metformin and metformin-associated anti-proliferative activity in VSMCs is, at least, partially dependent on PGC-1β. Our data show that PGC-1β is a critical component in regulating DNA replication, VSMC proliferation and vascular lesion formation, suggesting that PGC-1β may emerge a novel therapeutic target for control of proliferative vascular diseases.
Journal of Biological Chemistry 12/2012; · 4.77 Impact Factor
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ABSTRACT: OBJECTIVE: Endothelial cell (EC) inflammatory status is critical to many vascular diseases. Emerging data demonstrate that mutations of Krüppel-like factor-11 (KLF11), a gene coding maturity-onset diabetes mellitus of the young type 7 (MODY7), contribute to the development of neonatal diabetes mellitus. However, the function of KLF11 in the cardiovascular system still remains to be uncovered. In this study, we aimed to investigate the role of KLF11 in vascular endothelial inflammation. METHODS AND RESULTS: KLF11 is highly expressed in vascular ECs and induced by proinflammatory stimuli. Adenovirus-mediated KLF11 overexpression inhibits expression of tumor necrosis factors-α-induced adhesion molecules. Moreover, small interfering RNA-mediated KLF11 knockdown augments the proinflammatory status in ECs. KLF11 inhibits promoter activity of adhesion molecules induced by tumor necrosis factor-α and nuclear factor-κB p65 overexpression. Mechanistically, KLF11 potently inhibits nuclear factor-κB signaling pathway via physical interaction with p65. Furthermore, KLF11 knockdown results in increased binding of p65 to vascular cell adhesion molecule-1 and E-selectin promoters. At the whole organism level, KLF11(-/-) mice exhibit a significant increase in leukocyte recruitment to ECs after lipopolysaccharide administration. CONCLUSIONS: Taken together, our data demonstrate for the first time that KLF11 is a suppressor of EC inflammatory activation, suggesting that KLF11 constitutes a novel potential molecular target for inhibition of vascular inflammatory diseases.
Arteriosclerosis Thrombosis and Vascular Biology 10/2012; · 6.37 Impact Factor
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ABSTRACT: The Hippo-Yap (Yes-associated protein) signaling pathway has emerged as one of the critical pathways regulating cell proliferation, differentiation, and apoptosis in response to environmental and developmental cues. However, Yap1 roles in vascular smooth muscle cell (VSMC) biology have not been investigated. VSMCs undergo phenotypic switch, a process characterized by decreased gene expression of VSMC contractile markers and increased proliferation, migration, and matrix synthesis. The goals of the present studies were to investigate the relationship between Yap1 and VSMC phenotypic switch and to determine the molecular mechanisms by which Yap1 affects this essential process in VSMC biology. Results demonstrated that the expression of Yap1 was rapidly up-regulated by stimulation with PDGF-BB (a known inducer of phenotypic switch in VSMCs) and in the injured vessel wall. Knockdown of Yap1 impaired VSMC proliferation in vitro and enhanced the expression of VSMC contractile genes as well by increasing serum response factor binding to CArG-containing regions of VSMC-specific contractile genes within intact chromatin. Conversely, the interaction between serum response factor and its co-activator myocardin was reduced by overexpression of Yap1 in a dose-dependent manner. Taken together, these results indicate that down-regulation of Yap1 promotes VSMC contractile phenotype by both up-regulating myocardin expression and promoting the association of the serum response factor-myocardin complex with VSMC contractile gene promoters and suggest that the Yap1 signaling pathway is a central regulator of phenotypic switch of VSMCs.
Journal of Biological Chemistry 03/2012; 287(18):14598-605. · 4.77 Impact Factor
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ABSTRACT: Gluconeogenesis contributes to insulin resistance in type 1 and type 2 diabetes, but its regulation and the underlying molecular mechanisms remain unclear. Recently, calcium-regulated heat-stable protein 1 (CARHSP1) was identified as a biomarker for diabetic complications. In this study, we investigated the role of CARHSP1 in hepatic gluconeogenesis. We assessed the regulation of hepatic CARHSP1 expression under conditions of fasting and refeeding. Adenovirus-mediated CARHSP1 overexpression and siRNA-mediated knockdown experiments were performed to characterize the role of CARHSP1 in the regulation of gluconeogenic gene expression. Here, we document for the first time that CARHSP1 is regulated by nutrient status in the liver and functions at the transcriptional level to negatively regulate gluconeogenic genes, including the glucose-6-phosphatase catalytic subunit (G6Pc) and phosphoenolpyruvate carboxykinase 1 (PEPCK1). In addition, we found that CARHSP1 can physically interact with peroxisome proliferator-activated receptor-α (PPARα) and inhibit its transcriptional activity. Both pharmacological and genetic ablations of PPARα attenuate the inhibitory effect of CARHSP1 on gluconeogenic gene expression in hepatocytes. Our data suggest that CARHSP1 inhibits hepatic gluconeogenic gene expression via repression of PPARα and that CARHSP1 may be a molecular target for the treatment of diabetes.
Journal of Biological Chemistry 11/2011; 286(47):40584-94. · 4.77 Impact Factor
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ABSTRACT: Gluconeogenesis contributes to insulin resistance in type 1 and type 2 diabetes, but its regulation and the underlying molecular
mechanisms remain unclear. Recently, Calcium-Regulated Heat-Stable Protein-1 (CARHSP1) was identified as a biomarker for diabetic
complications. In this study, we investigated the role of CARHSP1 in hepatic gluconeogenesis. We assessed the regulation of
hepatic CARHSP1 expression under conditions of fasting and refeeding. Adenovirus-mediated CARHSP1 over-expression and siRNA-mediated
knockdown experiments were performed to characterize the role of CARHSP1 in the regulation of gluconeogenic gene expression.
Here, we documented for the first time that CARHSP1 is regulated by nutrient status in the liver and functions at the transcriptional
level to negatively regulate gluconeogenic genes, including the glucose-6-phosphatase catalytic subunit (G6Pc) and phosphoenolpyruvate
carboxykinase-1 (PEPCK1). In addition, we found that CARHSP1 can physically interact with peroxisome proliferator-activated
receptor-α(PPARα) and inhibit its transcriptional activity. Both pharmacological and genetic ablations of PPARα attenuate
the inhibitory effect of CARHSP1 on gluconeogenic gene expression in hepatocytes. Our data suggest that CARHSP1 inhibits hepatic
gluconeogenic gene expression via repression of PPARα, and also that CARHSP1 may be a molecular target for the treatment of
diabetes.
Journal of Biological Chemistry 10/2011; · 4.77 Impact Factor
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ABSTRACT: The role of microRNA-1 (miR-1) has been studied in cardiac and skeletal muscle differentiation. However, it remains unexplored in vascular smooth muscle cells (SMCs) differentiation. The aim of this study was to uncover novel targets of and shed light on the function of miR-1 in the context of embryonic stem cell (ESC) differentiation of SMCs in vitro. miR-1 expression is steadily increased during differentiation of mouse ESC to SMCs. Loss-of-function approaches using miR-1 inhibitors uncovered that miR-1 is required for SMC lineage differentiation in ESC-derived SMC cultures, as evidenced by downregulation of SMC-specific markers and decrease of derived SMC population. In addition, bioinformatics analysis unveiled a miR-1 binding site on the Kruppel-like factor 4 (KLF4) 3' untranslated region (3'UTR), in a region that is highly conserved across species. Consistently, miR-1 mimic reduced KLF4 3'UTR luciferase activity, which can be rescued by mutating the miR-1 binding site on the KLF4 3'UTR in the reporter construct. Additionally, repression of the miR-1 expression by miR-1 inhibitor can reverse KLF4 downregulation during ESC-SMC differentiation, which subsequently inhibits SMC differentiation. We conclude that miR-1 plays a critical role in the determination of SMC fate during retinoid acid-induced ESC/SMC differentiation, which may indicate that miR-1 has a role to promote SMC differentiation.
Stem cells and development 02/2011; 20(2):205-10. · 4.15 Impact Factor
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Yuqing Lou,
Jielin Liu,
Yao Li,
Ya Liu,
Zuoguang Wang,
Kuo Liu,
Hai Wu,
Qiuli Niu,
Wei Gu, Yanhong Guo,
Zhizhong Li,
Shaojun Wen
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ABSTRACT: The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.
This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059-1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121-1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059-2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056-1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258-2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.
We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.
PLoS ONE 01/2011; 6(4):e18590. · 4.09 Impact Factor
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ABSTRACT: Identification of individuals in the early stage of heart failure (HF) may allow earlier initiation of disease-modifying treatment. We evaluated concentrations of the growth differentiation factor (GDF)-15 at different stages and its potential screening value in 208 subjects. Plasma GDF-15 was measured by using an enzyme-linked immunosorbent assay. GDF-15 was positively correlated with the stages of HF (r=0.804, p<0.001). In distinguishing patients with stage B HF, the area under the curve was 0.873 (p<0.001). These findings indicate that GDF-15 concentration was elevated with the progressing stages of HF and might have potential screening implications for stage B HF.
Biomarkers 12/2010; 15(8):671-6. · 2.21 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVES: Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway. Methods AND RESULTS: In in vitro studies, neonatal cardiac myocytes were isolated and cultured. Incubation of cultured cardiomycytes with angiotensin II (Ang II) inhibited gene expression of Mfn2; induced cell hypertrophy and protein synthesis; and activated protein kinase Akt. Pretreatment of cells with AdMfn2-a replication-deficient adenoviral vector encoding rat Mfn2 gene-upregulated Mfn2 expression and subsequently attenuated Ang II-induced cell hypertrophy; protein synthesis; and Akt activation. In in vivo studies, direct gene delivery of AdMfn2 into myocardium decreased the infusion of Ang II-induced atrial natriuretic factor (ANF, a hypertrophic marker) expression and cardiomyocyte cross-sectional area. Consistently, upregulation of Mfn2 in myocardium decreased the thicknesses of anterior and posterior walls of left ventricle (LV) and the ratio of LV mass/body weight in Ang II-treated rats. Of note, AdGFP (control for AdMfn2) did not affect the effects of Ang II in vitro or in vivo. CONCLUSIONS: Upregulation of Mfn2 inhibits Ang II-induced myocardial hypertrophy. In this process, inhibition of Akt activation seems to play a significant role. These findings indicate Mfn2 is a critical protein in modulating myocyte hypertrophy.
Journal of Cardiovascular Pharmacology and Therapeutics 11/2010; 16(2):205-11. · 1.75 Impact Factor
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ABSTRACT: Nitroalkene derivatives of nitro-linoleic acid (LNO(2)) and nitro-oleic acid (OA-NO(2)) are nitrated unsaturated fatty acids that can be detected in healthy human plasma, red blood cells and urine. It has been shown that nitroalkenes have potent anti-inflammatory properties in multiple disease models. In the present study, we are the first to investigate the apoptotic effects of nitroalkenes in rat aortic smooth muscle cells (RASMCs). We observed that nitroalkenes induce RASMCs apoptosis in a dose-dependent manner. In addition, nitroalkenes stimulate extrinsic caspase-8 and intrinsic caspase-9 activity to trigger the caspase-3 apoptotic signaling cascade, resulting in RASMCs death. Furthermore, the pro-apoptotic protein, Bad was upregulated and antiapoptotic protein, Bcl-xl was downregulated during nitroalkene-induced apoptosis. These results demonstrate that nitroalkenes can induce RASMCs apoptosis via stimulation of caspase activity and the regulation of apoptotic protein expression levels.
Biochemical and Biophysical Research Communications 06/2010; 397(2):239-44. · 2.48 Impact Factor
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ABSTRACT: Previous studies of job strain and coronary heart disease (CHD) have produced mixed findings. We aimed to examine the association between job stress evaluated by the effort-reward imbalance (ERI) model and coronary atherosclerosis assessed by coronary angiography in a Chinese sample.
Three-hundred twenty participants accepting coronary angiography for the first time were enrolled in series. Job stressors were evaluated by the ERI model. The presence and severity of CHD were assessed by measuring the coronary artery stenosis (the presence of >50% luminal stenosis in one or more major coronary arteries). The association between job stressors and CHD was examined by multivariate analysis.
Compared with the low-level group, high-level effort, overcommitment, and ERI increased CHD risk with odds ratio (OR) 2.5 (95% confidence interval (CI): 1.2-5.0), 2.5 (95% CI: 1.2-5.0), 2.4 (95% CI: 1.2-4.9), respectively, after adjustment for confounders. They were also significantly positively correlated with the complexity of coronary artery lesions, respectively. Dose-response relationships were observed.
ERI was associated with coronary artery lesions in a sample of Chinese workers. Longitudinal research and interventional designs are needed to confirm the mechanism and to provide evidence for the prevention of CHD.
American Journal of Industrial Medicine 03/2010; 53(7):655-61. · 1.63 Impact Factor
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ABSTRACT: MicroRNAs(miRNAs) are important cellular components and their dysfunction is associated with various diseases. Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases. Although several miRNAs are reported to be associated with AMI, more novel miRNAs are needed to further investigate and improve certainty
We applied a well-established acute myocardial infarction rat model and performed miRNAs microarray experiments upon the myocardium tissue of rats with AMI and under sham control. We identified the differentially expressed miRNAs and analyzed the function of miRNA targets, transcription factors, and host genes based on bioinformatics.
As a result, the levels of expression of seventeen miRNAs significantly deregulated, of which four miRNAs were further validated by qRT-PCR. In addition, we observed that the transcription factors, targets, and host genes of these deregulated miRNAs are enriched in cardiovascular-related functions.
We found that the miRNAs expression level altered in rats with AMI and differentially expressed miRNAs may be novel biomarkers of AMI.
BMC Cardiovascular Disorders 03/2010; 10:11. · 1.52 Impact Factor
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ABSTRACT: This study was to examine the association between job stress and coronary heart disease (CHD) in a Chinese population.
The 388 participants aged 30 to 70 yr who received coronary angiography for suspected or known ischemic heart disease were enrolled in this series, which included 292 CHD cases and 96 controls. The job stress before CHD onset was measured by the effort-reward imbalance (ERI) model.
In the results, compared with the baseline, high ERI, high extrinsic effort or high overcommitment increased the risk of CHD with odds ratios (OR) of 2.8, 2.7 and 2.8 respectively after adjustment for the traditional CHD risk factors, such as age, gender, primary hypertension, diabetes mellitus, hyperlipidemia, smoking, body mass index, CHD family history, educational level, and marital status. The combination of high ERI and high overcommitment led to the highest risk of CHD with adjusted OR 5.5. However, high reward reduced the risk of CHD with an adjusted OR of 0.4 in comparison to low reward. Dose-response relationships were also observed.
Job stress evaluated by the ERI model significantly increased the risk of CHD, and it may be an important risk factor independent of the traditional risk factors of CHD in the Chinese population.
Journal of Occupational Health 02/2009; 51(2):107-13. · 1.55 Impact Factor
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ABSTRACT: It has been reported that increasingly microRNAs are associated with diseases. However, the patterns among the microRNA-disease associations remain largely unclear. In this study, in order to dissect the patterns of microRNA-disease associations, we performed a comprehensive analysis to the human microRNA-disease association data, which is manually collected from publications. We built a human microRNA associated disease network. Interestingly, microRNAs tend to show similar or different dysfunctional evidences for the similar or different disease clusters, respectively. A negative correlation between the tissue-specificity of a microRNA and the number of diseases it associated was uncovered. Furthermore, we observed an association between microRNA conservation and disease. Finally, we uncovered that microRNAs associated with the same disease tend to emerge as predefined microRNA groups. These findings can not only provide help in understanding the associations between microRNAs and human diseases but also suggest a new way to identify novel disease-associated microRNAs.
PLoS ONE 02/2008; 3(10):e3420. · 4.09 Impact Factor
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Lina Wu,
Zhixin Li,
Yingmei Zhang,
Pei Zhang,
Xiaohui Zhu,
Jing Huang,
Teng Ma,
Tian Lu,
Quansheng Song,
Qian Li, Yanhong Guo,
Jian Tang,
Dalong Ma,
Kuang-Hueih Chen,
Xiaoyan Qiu
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ABSTRACT: Hyperplasia suppressor gene (HSG), also called human mitofusin 2, is a novel gene that markedly suppresses the cell proliferation of hyperproliferative vascular smooth muscle cells from spontaneously hypertensive rat arteries. This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. In this report, we showed that an adenovirus vector encoding human HSG (Ad5-hHSG) had an antitumor activity in a wide range of cancer cell lines. We further focused on the lung cancer cell line A549 and the colon cancer cell line HT-29 and then observed that Ad5-hHSG induced apoptosis both in vitro and in vivo. Confocal laser scanning microscopy and electron microscopy revealed that cells infected with Ad5-hHSG formed dose-dependent perinuclear clusters of fused mitochondria. Adenovirus-mediated hHSG overexpression induced apoptosis, cell cycle arrest, mitochondrial membrane potential (DeltaPsim) reduction and release of cytochrome c, caspase-3 activation, and cleavage of PARP in vitro. Overexpression of hHSG also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. In addition, Ad5-hHSG increased the sensitivity of these cell lines to two chemotherapeutic agents, VP16 and CHX, and radiation. These results suggest that Ad5-hHSG may serve as an effective therapeutic drug against tumors.
Molecular Cancer Therapeutics 02/2008; 7(1):222-32. · 5.23 Impact Factor
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ABSTRACT: Previous studies have shown that mitofusin 2 (Mfn-2) (or hyperplasia suppressor gene [HSG]) inhibits vascular smooth muscle cell (VSMC) proliferation. Here, we demonstrate that Mfn-2 is a primary determinant of VSMC apoptosis. First, oxidative stress with H2O2, inhibition of protein kinase C with staurosporine, activation of protein kinase A with forskolin, and serum deprivation concurrently elevate Mfn-2 expression and induce VSMC apoptosis. Second, overexpression of Mfn-2 also triggers apoptosis of VSMCs in culture and in balloon-injured rat carotid arteries, thus contributing to Mfn-2-mediated prevention of neointima formation after angioplasty. Third, Mfn-2 silencing protects VSMCs against H2O2 or Mfn-2 overexpression-induced apoptosis, indicating that upregulation of Mfn-2 is necessary and sufficient for oxidative stress-mediated VSMC apoptosis. The Mfn-2 proapoptotic effect is independent of its role in mitochondrial fusion but mainly mediated by inhibition of Akt signaling and the resultant activation of the mitochondrial apoptotic pathway, as manifested by decreased Akt phosphorylation, increased mitochondrial Bax/Bcl-2 ratio, cytochrome c release, and activation of caspases-9 and caspase-3. Furthermore, Mfn-2-induced apoptosis was blocked by overexpression of an active phosphoinositide 3-kinase mutant or Bcl-xL or inhibition of caspase-9 but not caspases-8. Thus, in addition to its antiproliferative effects, Mfn-2 constitutes a primary determinant of VSMC apoptosis.
Circulation Research 12/2007; 101(11):1113-22. · 9.49 Impact Factor
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ABSTRACT: Angiopoietin-I (Ang I) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. In the current study, we tested the hypothesis that co-expression of AngI and VEGF could have an effect on development of leakage-resistant vessels.
Expression plasmids, pcD2 (control plasmid), pcD2/AngI, pcD2NEGF121, or pcD2/AngI +pcD2NEGF121, were injected intramuscularly into an ischaemic hindlimb rat model, followed by electroporation. Collateral vessel development and skeletal muscle atrophy were assessed before and 7, 14, 28 days after treatment. Capillary density was significantly increased in the rats transfected with AngI or VEGF compared with that in the rats transfected with pcD2 alone (P < 0.05). Rats transfected with AngI + VEGF had the highest capillary density (P < 0.05). The mean perimeter ratio of ligated hindlimb to non-ligated hindlimb was lower with pcD2 treatment rats compared with that in the rats transfected with AngI, VEGF or AngI +VEGF (P < 0.01). Limb necrosis was observed in two of 33 control rats, but none in the AngI and/orVEGF gene-transferred rats. The amount of extravasated Evans blue in rat ligated hindlimb muscle (7 days after treatment) treated with both AngI and VEGF was significantly less compared with that in the rats transfected with VEGF alone (P < 0.01).
The current study demonstrated that co-expression of AngI and VEGF genes in the ischaemic muscle effectively develops leakage-resistant vessels in the rat model. Therefore, this approach may provide a more appropriate therapeutic strategy in ischaemic vascular diseases.
Acta cardiologica 04/2006; 61(2):145-53. · 0.61 Impact Factor
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Hua Yan, Yanhong Guo,
Peng Zhang,
Lingyun Zu,
Xiaoyan Dong,
Li Chen,
Jianwei Tian,
Xiaolong Fan,
Nanping Wang,
Xiaobing Wu,
Wei Gao
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ABSTRACT: Recombinant adeno-associated virus serotype 2 (rAAV2) vector has been widely employed for gene therapy. Recent progress suggests that the new serotypes of AAV showed a better performance than did AAV2 in normal tissues. Here, we evaluate the potential role of human vascular endothelial growth factor (VEGF) gene transfer using rAAV vector pseudotyped with serotype 1 capsid proteins (rAAV1) in the treatment of muscle ischemia. In ischemic skeletal muscles, the rAAV1-LacZ vector allowed higher level, broader distribution, and long-lasting gene expression compared with the rAAV2-LacZ vector. Muscle VEGF165 production following the rAAV1-VEGF165 vector injection was 5-10 times higher than that following the rAAV2-VEGF165 vector injection. VEGF165 production mediated by the rAAV1-VEGF165 vector stimulated a large set of neovascularization with relatively mature vascular structures and enhanced muscle regeneration in the ischemic skeletal muscles. Thus, the rAAV1-VEGF165 vector mediated gene transfer may be a therapeutic approach to peripheral vascular diseases.
Biochemical and Biophysical Research Communications 11/2005; 336(1):287-98. · 2.48 Impact Factor
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ABSTRACT: Molecular Therapy (2005) 11, S247|[ndash]|S247; doi: 10.1016/j.ymthe.2005.07.177
637. Recombinant Adeno-Associated Viral Vector 2-Mediated Gene Transfer of VEGF165 Induces Neovascular Formation and Improves Blood Flow in Chronic Ischemic Swine Myocardium
Xiaoli Deng1, Xiaobing Wu2, Jie Jiang3, Yanhong Guo1, Lingyun Zu1 and Wei Gao11Cardiology of Department, Peking University Third Hospital, Beijing, China2AGTC Gene Technology Company Ltd., Beijing, China3Cardiology of Department, Peking University First Hospital, Beijing, China
Molecular Therapy 04/2005; · 6.87 Impact Factor
