Yan-Kun Shi

Chengdu Military General Hospital, Hua-yang, Sichuan, China

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Publications (12)23.13 Total impact

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    ABSTRACT: This study aimed to investigate the association between microRNA-155 (miR-155) and the severity and extent of coronary stenotic lesions. We measured the miR-155 expression by real-time PCR in 110 consecutive patients undergoing coronary angiography for suspected coronary artery disease. The severity and extent of coronary stenotic lesions were evaluated on the basis of coronary angiography findings by the Gensini score. The miR-155 expression was significantly lower in 56 patients with coronary heart disease than those in 54 controls (P<0.01). The level of miR-155 in peripheral blood mononuclear cells or plasma was lower in patients with unstable angina pectoris and acute myocardial infarction than in patients with chest pain syndrome, whereas no statistically significant differences were observed between patients with stable angina pectoris and chest pain syndrome. Spearman's correlation analysis showed that the expression of miR-155 in plasma correlated positively with the expression in peripheral blood mononuclear cells. The levels of miR-155 in the patients with diseased vessels of two and three or more were significantly lower than in those with diseased vessel of zero and one. The levels of miR-155 were not significantly different among groups with diseased vessels of zero and one. miR-155 were associated negatively with Gensini scores (r=-0.663, P<0.001). The miR-155 expression was correlated significantly to age (r=-0.227), hypertension (r=-0.440), total cholesterol (r=0.239), high-density lipoprotein cholesterol (r=0.280), low-density lipoprotein cholesterol (r=-0.315), tobacco use (r=-0.363), angiotensin-converting enzyme inhibitor (r=-0.250), statins (r=-0.368), and high-sensitivity C-reactive protein (r=-0.515). miR-155 expression is associated inversely with complicated proatherogenic metabolic risk factors, and the severity of coronary stenotic lesions calculated by Gensini scores.
    Coronary artery disease 02/2014; · 1.56 Impact Factor
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    ABSTRACT: Macrophage apoptosis is a prominent feature of advanced atherosclerotic plaques. Here, we examined the hypothesis that the apoptotic machinery is regulated by microRNA-155 (miR-155). Constitutive expression of miR-155 was detected in RAW264.7 cells, which was increased following stimulation with oxidized low-density lipoprotein (OxLDL) in a dose- and time-dependent manner. OxLDL-treated RAW264.7 cells showed a marked time- and dose-dependent increase in apoptosis, which was suppressed in the presence of mimics and increased with antagonists of miR-155. Bioinformatics analysis revealed Fas-associated death domain-containing protein (FADD) as a putative target of miR-155. Luciferase reporter assay and Western blot further disclosed that miR-155 inhibits FADD expression by directly targeting the 3'-UTR region. We propose that miR-155 attenuates the macrophage apoptosis, at least in part, through FADD regulation, since forced expression of FADD blocked the ability of miR-155 to inhibit apoptosis. Our results collectively suggest that miR-155 attenuates apoptosis of OxLDL-mediated RAW264.7 cells by targeting FADD, supporting a possible therapeutic role in atherosclerosis.
    Molecular and Cellular Biochemistry 06/2013; · 2.33 Impact Factor
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    ABSTRACT: BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. METHODS AND RESULTS: EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100μg, twice per week for 4weeks) to ApoE(-/-) mice, starting after 12weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. CONCLUSION: EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis.
    International journal of cardiology 05/2013; · 6.18 Impact Factor
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    ABSTRACT: Knockdown of stromal interaction molecule 1 (STIM1) significantly suppresses neointima hyperplasia after vascular injury. Endothelial progenitor cells (EPCs) are the major source of cells that respond to endothelium repair and contribute to re-endothelialization by reducing neointima formation after vascular injury. We hypothesized that the effect of STIM1 on neointima hyperplasia inhibition is mediated through its effect on the biological properties of EPCs. In this study, we investigated the effects of STIM1 on the proliferation and migration of EPCs and examined the effect of STIM1 knockdown using cultured rat bone marrow-derived EPCs. STIM1 was expressed in EPCs, and knockdown of STIM1 by adenoviral delivery of small interfering RNA (siRNA) significantly suppressed the proliferation and migration of EPCs. Furthermore, STIM1 knockdown decreased store-operated channel entry 48h after transfection. Replenishment with recombinant human STIM1 reversed the effects of STIM1 knockdown. Our data suggest that the store-operated transient receptor potential canonical 1 channel is involved in regulating the biological properties of EPCs through STIM1. STIM1 is a potent regulator of cell proliferation and migration in rat EPCs and may play an important role in the biological properties of EPCs.
    Biochemical and Biophysical Research Communications 07/2010; 398(2):315-20. · 2.28 Impact Factor
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    ABSTRACT: Migration and proliferation of endothelial progenitor cells (EPCs) are the key mechanisms in re-endothelialization after vascular injury. Inhibitor of DNA binding-1 (Id1) function has been linked to the proliferation, migration, and senescence of cells, and studies have shed light on the relationship between Id1 and the biological functions of EPCs. On the basis of the available data concerning Id1 and the behavior of EPCs, we hypothesized that Id1 was an important regulator in modulating the migration and proliferation of EPCs. Culture of spleen-derived EPCs was done as previously described. Id1 was presented at low levels in EPCs. Id1 was localized predominantly in the cytoplasm, and was rapidly upregulated by stimulation with serum and vascular endothelial growth factor. The migration and proliferation of EPCs were extensively improved by overexpression of adenovirus-mediated exogenous Id1 and inhibited by silencing of endogenous Id1 in EPCs. These results suggest that Id1 has a direct role in regulation of the migration and proliferation in EPCs.
    Molecular and Cellular Biochemistry 09/2009; 335(1-2):19-27. · 2.33 Impact Factor
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    ABSTRACT: Endothelial dysfunction is associated with cardiovascular diseases. The Ca2+ influx occurring via activation of plasmalemma Ca2+ channels was shown to be critical in signaling the increase in endothelial permeability in response to a variety of permeability-increasing mediators. It has been reported that angiotensin II (AngII) could induce Ca2+ signaling in some cells, and transient receptor potential canonical 1 (TRPC1) had an important role in this process. The objective of this study was to examine the mechanism of AngII-induced Ca2+ entry and vascular endothelial hyperpermeability. Human umbilical vein endothelial cells (HUVECs) exposed to AngII exhibited dose-dependent increase in [Ca2+]i and endothelial permeability. Quantitative real-time RT-PCR and Western blotting showed that the level of TRPC1 expression had increased significantly at 12h and at 24h after treatment of HUEVCs with AngII. The expression of p65 was suppressed using an RNAi strategy. The results showed that the NF-κB signaling pathway and type-1 receptor of AngII was involved in AngII-induced TRPC1 upregulation. Moreover, knockdown of TRPC1 and NF-κB expression attenuates AngII-induced [Ca2+]i and endothelial permeability. NF-κB and TRPC1 have critical roles in AngII-induced Ca2+ entry and endothelial permeability.
    Peptides 01/2009; 30(7):1368-1373. · 2.52 Impact Factor
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    ABSTRACT: There is evidence to suggest that stromal interaction molecule 1 (STIM1) functions as a Ca2+ sensor on the endoplasmic reticulum, leading to transduction of signals to the plasma membrane and opening of store-operated Ca2+ channels (SOC). SOC have been detected in vascular smooth muscle cells (VSMCs) and are thought to have an essential role in the regulation of contraction and cell proliferation. We hypothesized that knockdown of STIM1 inhibits VSMC proliferation and suppresses neointimal hyperplasia. We examined the effect of the knockdown of STIM1 using a rat balloon injury model and cultured rat aortic VSMCs. Interestingly, knockdown of rat STIM1 by adenovirus delivery of small interfering RNA (siRNA) significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at 14 days after injury. The re-expression of human STIM1 to smooth muscle reversed the effect of STIM1 knockdown on neointimal formation. Rat aortic VSMCs were used for the in vitro assays. Knockdown of endogenous STIM1 significantly inhibited proliferation and migration of VSMCs. Moreover, STIM1 knockdown induced cell-cycle arrest in G0/G1 and resulted in a marked decrease in SOC. Replenishment with recombinant human STIM1 reversed the effect of siRNA knockdown. These results suggest STIM1 has a critical role in neointimal formation in a rat model of vascular injury. STIM1 may represent a novel therapeutic target in the prevention of restenosis after vascular interventions.
    Cardiovascular research 01/2009; 81(4):660-8. · 5.81 Impact Factor
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    ABSTRACT: To investigate the relationship between the plasma macrophage migration inhibitory factor (MIF), activator protein-1 (AP-1) and MMP-9 concentrations and the severity of coronary artery lesions in coronary heart disease (CHD) patients. Patients were divided into normal controls (n = 35), stable angina pectoris (SAP, n = 32) and acute coronary syndrome (ACS, n = 75) according to the coronary angiography (CAG), clinical and laboratory examinations. The CAG severity and extent of coronary lesions were analyzed by means of Gensini coronary score system. Enzyme linked immunosorent assay was used to measure the plasma MIF, AP-1 and MMP-9 concentrations. Plasma MIF, AP-1 and MMP-9 concentrations were significant increased in CHD patients [MIF: (14.97 +/- 2.11) microg/L, AP-1: 1.43 +/- 0.33, MMP-9: (1.48 +/- 0.14) microg/L] compared to those in control group [MIF: (9.07 +/- 1.28) microg/L, AP-1: 0.71 +/- 0.13, MMP-9: (1.01 +/- 0.07) microg/L, all P < 0.05]. The MIF, AP-1 and MMP-9 concentrations in ACS group [MIF: (16.66 +/- 2.56) microg/L, AP-1: 1.56 +/- 0.22, MMP-9: (1.58 +/- 0.14) microg/L] were also significant higher than those in SAP group [MIF: (11.01 +/- 2.12) microg/L, AP-1: 1.04 +/- 0.25, MMP-9: (1.25 +/- 0.07) microg/L, all P < 0.05] and there was significant positive correlation between MIF, AP-1 and MMP-9 concentrations and the Gensini score of coronary artery lesions (all P < 0.05). AP-1 was positively correlated with MMP-9 in CHD patients (P < 0.05). Plasma MIF, AP-1 and MMP-9 concentrations were positively correlated to the severity of coronary lesions in CHD patients. Higher MIF, AP-1 and MMP-9 concentrations in ACS patients than in SAP patients might suggest higher plaque instability in ACS patients.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2008; 36(10):912-5.
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    ABSTRACT: To investigate the relation between activator protein-1 (AP-1) and coronary atherosclerotic changes and the potential role of AP-1 in the stabilization of atherosclerotic plaques in patients with coronary heart disease (CHD). 142 patients were included in this study and divided into CHD group (107) and control group (35) according to coronary angiography (CAG). The CHD group was further divided into a stable angina pectoris (SAP) group (32) and an acute coronary syndrome (ACS) group (75) according to the clinical manifestations. In addition, the CHD group was divided into A type group, B type group and C type group according to the standard of ACC/AHA coronary change in 1988. Meanwhile, the CHD group was further divided into light stenosis group, moderate stenosis group and severe stenosis group according to the degree of coronary lesion. The lysate of cells was obtained through lysis of the leucocytes from peripheral blood with cell lysis buffer. The amount of Phospho-c-Jun in lysate was measured with enzyme-linked immunosorbent assay (ELISA). The results were demonstrated with absorbance, which reflects the amount of AP-1. The main coronary changes in the SAP group were A type (68.7%) and the changes were mainly of light degree (53.1%); the main coronary changes in the ACS group were B type (52.0%) or C type (37.3%) and the changes were mainly of heavy degree (66.7%). The absorbance of Phospho-c-Jun in CHD group was significantly higher than that in the control subjects (1.43 +/- 0.33 vs 0.71 +/- 0.13, P < 0.001). The absorbance of Phospho-c-Jun in the ACS group was significantly higher than that in the SAP group (1.56 +/- 0.28 vs 1.14 +/- 0.25, P < 0.001). The absorbance of Phospho-c-Jun increased gradually from A type group to C type group (1.18 +/- 0.27 vs 1.42 +/- 0.26 vs 1.71 +/- 0.27, P < 0.001) and from light stenosis group to severe stenosis group (1.09 +/- 0.20 vs 1.37 +/- 0. 26 vs 1.60 +/- 0.29, P < 0.001). There is a significant relationship between AP-1 and coronary atherosclerotic changes. AP-1 may be a factor that can predict coronary arteriosclerotic progression and stability of the plaque.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 08/2008; 47(7):545-7.
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    ABSTRACT: To observe the relationship between murine double minute 2 (mdm2) expression and AngII and ceramide induced human umbilical endothelial cells apoptosis. Human umbilical endothelial cells (ECs) were cultured in vitro and treated with angiotensin II alone or in combination with losartan (an inhibitor of AT1), PD123319 (an inhibitor of AT2) and FB1 (an inhibitor of ceramidase) respectively. ECs were also treated with different doses of C2-ceramide. The apoptosis of ECs was detected with Tunel, the mdm2 mRNA and protein expressions were measured with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. PD123319 and FB1 but not losartan inhibited AngII induced ECs apoptosis and down-regulated the AngII induced increased mdm2 expressions. C2-ceramide also induces ECs apoptosis and down-regulated mdm2 expressions at protein and mRNA levels in a dose-dependent manner. AngII binding with AT2 induces ECs apoptosis via ceramide. AngII and ceramide induce EC apoptosis by inhibiting mdm2.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 11/2007; 35(10):945-8.
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    ABSTRACT: Angiotensin II is an important pro inflammation factor in the cardiovascular system. This experiment is aimed to study the effects of angiotensin II on inducible nitric oxide synthase expression in human umbilical endothelial cells. Human umbilical endothelial cells were cultured in vitro and treated with angiotensin II alone or in combination with AT1, AT2 and NF-kappaB inhibitors respectively. The inducible nitric oxide synthase expressions at protein and mRNA levels were measured with Western blot and reverse transcription-polymerase chain reaction (RT-PCR), and the activity of NF-kappaB was analyzed with EMSA. Angiotensin II up-regulated inducible nitric oxide synthase expressions at the protein and mRNA levels at 5 h (P < 0.05), the activity of NF-kappaB was enhanced at 2 h (P < 0.05). These effects could be blocked by AT1 and NF-kappaB inhibitors but not by AT2 inhibitor. Angiotensin II can upregulate the expression of inducible nitric oxide synthase through NF-kappaB pathway in human umbilical endothelial cells. AT1, other than AT2, play a key role in this process.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 07/2006; 34(7):647-50.
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    ABSTRACT: The cytokine tumor necrosis factor (TNF) alpha has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. It is essential to study the changes of plasma levels of TNF alpha and matrix metalloproteinase-2,3,9 (MMP-2,3,9) expressions in myocardium during congestive heart failure (CHF). Plasma levels of TNF alpha were measured with enzyme-linked immunoassay in CHF patients of various degrees and in healthy controls. Using Western blotting assay, we detected the protein expressions of MMP-2,3,9 on myocardial tissue in CHF patients and in healthy controls. Cardiac function parameters were measured with echocardiographic studies. Plasma levels of TNF alpha increased significantly in patients with CHF (P < 0.05 or < 0.01). The protein expressions of MMP-2,3,9 were significantly higher in patients with CHF than in controls (P < 0.05 or < 0.01). The higher the degree of CHF, the greater the numbers of expressions. No changes of MMP-2 could be found between the controls and CHF patients of NYHA II. There was a positive correlation between plasma levels of TNF alpha and the protein expressions of MMP-2,3,9 (P < 0.01 or < 0.001). It is suggested that alterations of TNF alpha may stimulate the expressions of MMPs, contribute to myocardial remodeling and lead to the development and progression of congestive heart failure. These changes may induce a direct effect on the progression and deterioration of heart failure.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 11/2004; 43(11):828-31.