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ABSTRACT: Persistent fibroblast activation in wound repair is believed to be the key reason for fibrosis and transforming growth factor (TGF)β is considered as one of the key mediators for the fibrogenic response, with the detailed mechanism largely unknown. Here we found that TGFβ1 treatment could induce a significant increase of endogenous TGFβ1 expression by enhancing the mRNA stability in cardiac fibroblasts. Further study revealed that TGFβ1 treatment translocated the nuclear HuR into cytoplasm, which in turn bound the ARE in the 3'UTR of TGFβ1 and increased the mRNA stability as seen from the RNA-IP and reporter assay. Knockdown of HuR decreased the endogenous expression of TGFβ1 under exogenous TGFβ1 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. Our study here established a TGFβ1/HuR feedback circuit regulating the fibrogenic response in fibroblasts, and targeting this feedback loop is of great potential to control fibrosis.
Cellular signalling 03/2012; 24(7):1426-32. · 4.09 Impact Factor
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Dongjuan Wang,
Haichang Wang,
Peng Luo,
Andrew Hwang,
Dongdong Sun,
Yabin Wang,
Zheng Zhang,
Nan Liu,
Shenxu Wang, Chengxiang Li,
Feng Cao
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ABSTRACT: Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs. In contrast, ghrelin pretreatment significantly improved proliferation and NO secretion, and inhibited cell apoptosis and secretion of cytokines in HCY-induced CMECs. In addition, Western blot assay showed that NF-κB (nuclear factor κB) and cleaved-caspase 3 expression were elevated, and PCNA (proliferating cell nuclear antigen) and eNOS (endothelial nitric oxide synthase) expression were decreased after treatment with HCY, which was significantly reversed by pretreatment with ghrelin. The data suggest that ghrelin inhibits HCY-induced CMEC dysfunction and inflammatory response, probably mediated by inhibition of NF-κB activation.
Cell Biology International 02/2012; 36(6):511-7. · 1.48 Impact Factor
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ABSTRACT: BACKGROUND: To investigate the efficacy and proposed mechanism of bone marrow mononuclear cells (BMMNCs) transplantation for diabetic and non-diabetic patients with ST-segment elevation myocardial infarction (STEMI). METHODS: One hundred and sixteen patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were divided into a diabetic group (n=51) and non-diabetic group (n=65). All of the patients received intracoronary injection of BMMNCs. RESULTS: Diabetes down-regulated IGF-1, IGFBP-5, VEGF, SDF-1, IL-6, IL-1α and TNF-α expression and affected the expression of Bmi-1, Gfi1, Tel and Hox-B4 which could prevent premature senescence and maintain the self-renewal capacity of stem cells. Event-free survival rates were not statistically different between the diabetic and non-diabetic group (80% vs. 72.5%, p=0.382). LV ejection fraction (LVEF) and wall motion score index (WMSI) were evaluated by echocardiography and found to be significantly improved in the non-diabetic group compared to the diabetic group over the 4-year follow-up period. Improved myocardial perfusion and reduced infarct size in the non-diabetic group compared to the diabetic group was verified using single-photon emission computed tomographic (SPECT) imaging. The non-diabetic group also had reduced anginal symptoms as assessed by changes in their Seattle Angina Questionnaire scores and Canadian Cardiovascular Society (CCS) Functional Angina classification. An improvement of 6-minute walk distance (6MWD) was also noted to be higher in the non-diabetic group during the follow-up period. CONCLUSION: This study indicates that the beneficial effect of BMMNCs transplantation for STEMI is less pronounced in diabetic patients. The mechanism is associated with decreased BMMNCs function in diabetic patients.
International journal of cardiology 02/2012; · 7.08 Impact Factor
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Dongdong Sun,
Jing Wang,
Yue Tian,
Kazim Narsinh,
Haichang Wang, Chengxiang Li,
Xiaowei Ma,
Yabing Wang,
Dongjuan Wang,
Chunhong Li,
Joseph C Wu,
Jie Tian,
Feng Cao
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ABSTRACT: Aims: To determine the effects of percutaneous coronary intervention (PCI) on cardiac perfusion, cardiac function, and quality of life in patients with chronic total occlusion (CTO) lesion in left anterior descending (LAD) coronary artery.Methods and Results: Patients (n=99) with CTO lesion in the LAD coronary artery who had successfully undergone PCI were divided into three groups based on the SPECT/CTCA fusion imaging: (a) no severe cardiac perfusion defects (n=9); (b) reversible cardiac perfusion defects (n=40); or (c) fixed cardiac perfusion defects (n=50). No statistical difference of perfusion abnormality was observed at 6 months and 1 year after PCI in group (a). In group (b), SPECT/CTCA fusion imaging demonstrated that cardiac perfusion abnormality was significantly decreased 6 month and 1 year after PCI. Left ventricular ejection fraction (LVEF) increased significantly at 6 months and 1 year follow up. Quality of life improved at 6 months and 1 year after PCI procedure. Moreover, patients in group (c) also benefited from PCI therapy: a decrease in cardiac perfusion abnormality, an increase in LVEF, and an improvement in quality of life. PCI of coronary arteries in addition to LAD did not significantly affect cardiac function and quality of life improvement in each group.Conclusions: PCI exerts functional and clinical benefits in patients with CTO lesion in LAD coronary artery, particularly in patients with reversible cardiac perfusion defects. SPECT/CTCA fusion imaging may serve as a useful tool to evaluate the outcomes of patients with CTO lesion in LAD coronary artery.
Theranostics. 01/2012; 2(8):788-800.
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ABSTRACT: Interfacial shear strengths or static frictions between carbon nanotubes (CNT) in contact at different cross angles are studied by using atomic mechanics. It is shown that the axial interfacial shear strengths between parallel CNTs in commensurate are two orders of magnitude greater than those in incommensurate. This strong chiral dependence is not surprising and is similar to that of the friction between two graphite basal planes. In contrast, we find that the interfacial shear strengths of crossly contacted CNT pairs are much less dependent upon chirality. The estimated values of interfacial shear strengths, ranging from 0.05 to 0.35 GPa, agree very well with experimentally measured results available in the literature. These results may thus be used as a basis for explaining the observed tension strengths of CNT bundles and films that are mainly bonded by van der Waals interactions and the mechanical behaviors of composite materials with highly concentrated CNTs.
Nanotechnology 02/2010; 21(11):115704. · 3.98 Impact Factor
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Feng Cao,
Dongdong Sun, Chengxiang Li,
Kazim Narsinh,
Li Zhao,
Xue Li,
Xuyang Feng,
Jun Zhang,
Yunyan Duan,
Jing Wang,
Dingjing Liu,
Haichang Wang
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ABSTRACT: To evaluate the safety profile and efficacy of bone marrow mononuclear cells (BMMNC) transplantation for ST-segment elevation myocardial infarction (STEMI) by assessing patients and their left ventricular function at up to 4 years follow-up.
Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were randomized to receive intracoronary injection of BMMNC (n = 41) or saline (n = 45). Left ventricular ejection fraction, as evaluated by UCG, was markedly improved at 6 months (0.484 +/- 0.5 vs. 0.457 +/- 0.6, P = 0.001), 1 year (0.482 +/- 0.7 vs. 0.446 +/- 0.6, P < 0.001), and 4 years (0.505 +/- 0.8 vs. 0.464 +/- 0.8, P < 0.001) after BMMNC transplant when compared with control group. However, the current cell therapy did not improve the myocardial viability of the infarcted area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant (0.263 +/- 0.007 in BMMNC group vs. 0.281 +/- 0.008 in control group, P = 0.10). During the follow-up period, one control group case (2.2%) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI. Also during follow-up, one death (2.2%) occurred in the control group, and one patient (2.4%) in the BMMNC group had transient acute heart failure.
This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI, and can lead to long-term improvement in myocardial function.
European Heart Journal 06/2009; 30(16):1986-94. · 10.48 Impact Factor
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ABSTRACT: Primary cultured rat aortic vascular smooth muscle cells (VSMCs) were exposed to different intensities of low-frequency electromagnetic fields (LFEMFs) at 20, 40, and 60 mT for different time periods (10, 20, and 30 minutes). Furthermore, osteopontin (OPN) mRNA and protein expressions were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Matrix metalloproteinase-2 (MMP-2) activity was measured using gelatin zymography. The results showed that the OPN mRNA and protein expressions and MMP-2 activity of VSMCs were inhibited by exposure to LFEMFs of different intensities in a dose-dependent manner (P < 0.05) but not in a time-dependent manner. In conclusion, exposure to LFEMFs of appropriate intensity for a suitable time period can result in the inhibition of the OPN expression and MMP-2 activity of VSMCs, indicating the potential prophylactic and therapeutic effects of LFEMFs on restenosis (RS) following percutaneous coronary intervention (PCI).
International Heart Journal 10/2008; 49(5):597-604. · 1.16 Impact Factor
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ABSTRACT: Low-density lipoprotein (LDL) is a major trigger of atherosclerotic lesions. Here we report the production of natural mouse IgM monoclonal antibodies (MAbs) against LDL with high specificity and activity, which could provide a potential value for research on lipid metabolism and atherosclerosis progression. BALB/c mice were raised in specific pathogen-free conditions and fed a high cholesterin diet; the splenocytes from these mice were directly fused with Sp2/0 myeloma cells using standard hybridoma production techniques. Resulting hybridomas producing anti-LDL antibodies were screened by enzyme-linked immunosorbent assay (ELISA) and isotyped. As a result, two hybridoma cell lines, named 5G8 and 2H7, were developed, which could secrete anti-LDL MAbs stably. Both of them belonged to the IgM subclass. The specificity of the MAb was determined based on its activity in Western blot and immunoprecipitation analysis.
Hybridoma (2005) 03/2008; 27(1):54-8. · 0.42 Impact Factor
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ABSTRACT: To assess the immediate- and long-term outcomes of stent supported coronary angioplasty in patients with severe left ventricular dysfunction.
Seventy-four consecutive patients with angiographic left ventricular ejection fractions < or = 40% underwent percutaneous coronary angioplasty, including 61 (81%) with stent back-up. Clinical follow-up (29.1 +/- 22.9 months) data were obtained in all clinically successful patients.
Angiographic success was achieved in 120 (89.5%) of 134 lesions. Clinical success was obtained in 66 (89.2%) patients with 1.4% procedure related mortality, 2.7% myocardial infarction and zero need of emergent bypass surgery. NYHA class reduction > or = 1 was seen in 29 (73%) of 40 successfully treated congestive heart failure patients at 6 months after the procedure. During long-term follow-up, 58 (87.9%) of 66 patients with clinical success were alive, including 44 (68.6%) free from cardiac events.
Patients with severe left ventricular dysfunction treated with stent supported PTCA experience a high rate of success, low procedure related mortality and satisfactory long-term survival.
Chinese medical journal 03/2002; 115(3):355-8. · 0.86 Impact Factor
