Chongqing Institute of Cardiology

Chongqing, China

Chongqing Institute of Cardiology

Chongqing, China
Time filter
Source Type

Zhang Y.,Chongqing Medical University | Zhang Y.,Chongqing Institute of Cardiology | Wang X.,Chongqing Medical University | Wang X.,Chongqing Institute of Cardiology | And 5 more authors.
Journal of Hypertension | Year: 2011

Objective: Abnormal vascular smooth muscle cell (VSMC) proliferation is involved in the development of vascular diseases. However, the mechanisms by which insulin exerts this effect are not completely known. We hypothesize that microRNAs might be involved in insulin-induced VSMC proliferation. Methods:VSMC proliferation was determined by [H]-thymidine incorporation; microRNAs were determined by microRNA chips and real-time PCR; and p21expression was determined by immunoblotting. Results: In this study, we found that insulin increased VSMC proliferation and miR-208 expression. Overexpression of miR-208 increased basal and insulin-mediated VSMC proliferation. Although a miR-208 inhibitor, by itself, had no effect on VSMC proliferation, it reduced the insulin-mediated cell proliferation. Moreover, miR-208 increased the transformation of cell cycle from G0/G1 phase to the S phase. Bioinformatics analysis found that p21, a member of the cyclin-dependent kinase (CDK)-inhibitory protein family, may be the target of miR-208. Insulin decreased p21 expression in VSMCs; transfection of miR-208 also decreased p21 protein expression. In the presence of miR-208 inhibitor, the inhibitory effect of insulin on p21 expression in VSMCs was partially blocked. The interaction between miR-208 and p21 was direct. Using a luciferase reporter with entire wild-type p21 3′UTR or a mutant p21 3′UTR in HEK293 cells, we found that miR-208 decreased but neither miR-208 mimic nor the mutant p21 3′UTR had any significant effect on the luciferase activity. Conclusion: This study indicates that miRNAs, miR-208, in particular, are involved in the insulin-induced VSMC proliferation via downregulation of its potential target, p21, a key member of CDK-inhibitory protein family. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Wang Z.,Georgetown University | Zeng C.,Chongqing Medical University | Villar V.A.M.,Chongqing Institute of Cardiology | Chen S.-Y.,University of Georgia | And 12 more authors.
Hypertension | Year: 2016

The influence of a single gene on the pathogenesis of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G-protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4γ142V in mice results in hypertension because of impaired dopamine D1 receptor. Signaling through dopamine D1 receptor and angiotensin II type I receptor (AT1R) reciprocally modulates renal sodium excretion and blood pressure. Here, we demonstrate the ability of the hGRK4γ142V to increase the expression and activity of the AT1R. We show that hGRK4γ142V phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. AT1R blockade and the deletion of the Agtr1a gene normalize the hypertension in hGRK4γ142V mice. These findings illustrate the unique role of GRK4 by targeting receptors with opposite physiological activity for the same goal of maintaining blood pressure homeostasis, and thus making the GRK4 a relevant therapeutic target to control blood pressure. © 2015 American Heart Association, Inc.

Chen K.,Chongqing Medical University | Chen K.,Chongqing Institute of Cardiology | Fu C.,Chongqing Medical University | Fu C.,Chongqing Institute of Cardiology | And 19 more authors.
Hypertension | Year: 2014

G-protein-coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin-angiotensin system functions, cause sodium retention and increase blood pressure. Whether GRK4 and the angiotensin type 1 receptor (AT1R) interact in the aorta is not known. We report that GRK4 is expressed in vascular smooth muscle cells of the aorta. Heterologous expression of the GRK4γ variant 142V in A10 cells increased AT1R protein expression and AT1R-mediated increase in intracellular calcium concentration. The increase in AT1R expression was related to an increase in AT1R mRNA expression via the NF-κB pathway. As compared with control, cells expressing GRK4γ 142V had greater NF-κB activity with more NF-κB bound to the AT1R promoter. The increased AT1R expression in cells expressing GRK4γ 142V was also associated with decreased AT1R degradation, which may be ascribed to lower AT1R phosphorylation. There was a direct interaction between GRK4γ and AT1R that was decreased by GRK4γ 142V. The regulation of AT1R expression by GRK4γ 142V in A10 cells was confirmed in GRK4γ 142V transgenic mice; AT1R expression was higher in the aorta of GRK4γ 142V transgenic mice than control GRK4γ wild-type mice. Angiotensin II-mediated vasoconstriction of the aorta was also higher in GRK4γ 142V than in wild-type transgenic mice. This study provides a mechanism by which GRK4, via regulation of arterial AT1R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension. © 2013 American Heart Association, Inc.

Yang J.,Chongqing Medical University | Yang J.,Chongqing Institute of Cardiology | Han Y.,Chongqing Medical University | Han Y.,Chongqing Institute of Cardiology | And 11 more authors.
Life Sciences | Year: 2013

Aims Vascular inflammation is a key factor in the pathogenesis of diabetes-related vascular complications. Our previous study showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits high glucose-induced vascular smooth muscle cell proliferation, thus it may have beneficial effects in diabetes and its complications. However, the effect of EGCG on inflammation in diabetes is not known. In the present study, we investigated whether EGCG suppresses the vascular inflammation induced by high glucose in human umbilical vein endothelial cells (HUVECs). Main methods The inhibitory effect of EGCG on high glucose-induced up-regulation of the expression of vascular cell adhesion molecule 1 (VCAM-1) was measured using enzyme-linked immunosorbent, RT-PCR, immunoblotting and cell adhesion assays. The effect of EGCG on high glucose-induced nuclear factor-kappa B (NF-κB) activation was investigated by immunoblotting, immunofluorescence and electrophoretic mobility shift assays. Key findings High glucose increased VCAM-1 expression and enhanced the adhesion of monocytes to HUVECs. Pretreatment with EGCG in a concentration-dependent manner (1.0-50 μM) significantly attenuated these effects. High glucose (25 mM)-mediated vascular inflammation was blocked by PKC pseudosubstrate (PKC inhibitor 19-31) or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Stimulation with high glucose increased the NF-κB translocation from the cytoplasm to the nucleus, and increased IκB-α phosphorylation, decreased its expression, and in the presence of EGCG, the effect of high glucose on NF-κB and IκB-α were blocked. Significance EGCG suppresses high glucose-induced vascular inflammatory process via the inhibition of PKC and NF-κB activation in HUVECs, suggesting that EGCG may be a potential candidate for the treatment and prevention of diabetic vascular complications. © 2013 Elsevier Inc.

Li C.,Chongqing Medical University | Li C.,Chongqing Institute of Cardiology | Pei F.,Chongqing Medical University | Pei F.,Chongqing Institute of Cardiology | And 5 more authors.
Clinical Biochemistry | Year: 2012

Coronary artery disease and acute myocardial infarction (AMI) are the leading causes of death for both men and women. Serum cardiac-specific troponin level is now used for the "early" diagnosis of AMI. However, due to the "delayed" release of troponin, an earlier, more sensitive and specific biomarker is urgently demanded to further reduce AMI mortality. Recent studies have found that circulating microRNAs (miRNAs) are closely linked to myocardial injury. Due to the cell-specific physiological functions and the stability of miRNAs in plasma, serum, and urine, they are emerging as sensitive biomarkers of AMI. This review summarizes the latest insights into the identification and potential application of plasma and serum miRNAs as novel biomarkers for diagnosis and prognosis of AMI. © 2012 The Canadian Society of Clinical Chemists.

Yang J.,Chongqing Medical University | Yang J.,Chongqing Institute of Cardiology | Chen C.,Chongqing Medical University | Chen C.,Chongqing Institute of Cardiology | And 12 more authors.
Journal of Hypertension | Year: 2012

Background: The renin-angiotensin (Ang) system controls blood pressure, in part, by regulating renal tubular sodium transport. In the kidney, activation of the angiotensin II type 1 (AT 1) receptor increases renal sodium reabsorption, whereas the angiotensin II type 2 (AT 2) receptor produces the opposite effect. We hypothesized that the AT 2 receptor regulates AT1 receptor expression and function in the kidney. METHODS AND Results: In immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto rats, CGP42112, an AT 2 receptor agonist, decreased AT 1 receptor mRNA and protein expression (P < 0.05), as assessed by reverse transcriptase-polymerase chain reaction and immunoblotting. The inhibitory effect of the AT 2 receptor on AT 1 receptor expression was blocked by the AT 2 receptor antagonist, PD123319 (10 -6 mol/l), the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (10 -4 mol/l), or the nitric oxide-dependent soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (10 -5 mol/l), indicating that both nitric oxide and cyclic guanosine monophosphate (cGMP) were involved in the signaling pathway. Furthermore, CGP42112 decreased Sp1 serine phosphorylation and reduced the binding of Sp1 to AT 1 receptor DNA. Stimulation with Ang II (10 -11 mol/l per 30 min) enhanced Na-K-ATPase activity in RPT cells, which was prevented by pretreatment with CGP42112 (10 -7 mol/l per 24 h) (P < 0.05). The above-mentioned results were confirmed in RPT cells from AT 2 receptor knockout mice; AT 1 receptor expression and Ang II-stimulated Na +-K +-ATPase activity were greater in these cells than in RPT cells from wild-type mice (P < 0.05). AT 1/AT 2 receptors co-localized and co-immunoprecipitated in RPT cells; short-term CGP42112 (10 -7 mol/l per 30 min) treatment increased AT 1/AT 2 receptor co-immunoprecipitation (P < 0.05). Conclusions: These results indicate that the renal AT 2 receptor, via nitric oxide/cGMP/Sp1 pathway, regulates AT 1 receptor expression and function, which may be important in the regulation of sodium excretion and blood pressure. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Chen Y.,Chongqing Medical University | Chen Y.,Chongqing Institute of Cardiology | Asico L.D.,University of Maryland Baltimore County | Zheng S.,Chongqing Medical University | And 9 more authors.
Hypertension | Year: 2013

Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats. The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of either D1-like receptor or gastrin receptor inhibited Na-K-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor coimmunoprecipitated, which was increased after stimulation of either D1 receptor or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor increased the RPT cell membrane expression of the other receptor, effects that were not observed in spontaneously hypertensive rats. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCK BR and D1-like receptors (eg, D1 receptor) may play a role in the pathogenesis of hypertension. © 2013 American Heart Association, Inc.

Liu Y.,Chongqing Medical University | Liu Y.,Chongqing Institute of Cardiology | Chen K.,Chongqing Medical University | Chen K.,Chongqing Institute of Cardiology | And 8 more authors.
PLoS ONE | Year: 2013

Background:Aliskiren is a novel renin-angiotensin aldosterone system (RAAS) inhibitor, the combination therapy of aliskiren and amlodipine for blood pressure control have been reported recently. The primary objective of this analysis is to review recently reported randomized controlled trials (RCTs) to compare antihypertensive effects and adverse events between mono (amlodipine or aliskiren alone) and combination therapy of both medicines.Methods:Databases for the search included Pubmed, Embase and the Cochrane Central Register of Controlled Trials. Revman v5.0 statistical program was used to analyze the data. Weighted mean differences (WMD) with a 95% confidence interval (CI) were used for the calculation of continuous data, and relative risk (RR) with a 95% CI was used for dichotomous data.Results:We analyzed the data from 7 RCTs for a total of 6074 participants in this meta-analysis. We found that the aliskiren/amlodipine combination therapy had a stronger effect in lowering blood pressure as compared with the monotherapy using aliskiren (SBP: WMD = -10.42, 95% CI -13.03∼-7.82, P<0.00001; DBP: WMD = -6.60, 95% CI -7.22∼-5.97, P<0.00001) or amlodipine (SBP: WMD = -4.85, 95% CI -6.88∼-2.81, P<0.00001; DBP: WMD = -2.91, 95% CI -3.85∼-1.97, P<0.00001). No differences were found in terms of adverse events between combination therapy and monotherapy, except for the rates of peripheral edema and hypokalaemia which were significantly lower in the combination therapy than in the amlodipine monotherapy (RR = 0.78, 0.66∼0.92, P = 0.004; RR = 0.51, 0.27∼0.97, P = 0.04). Similar antihypertensive effects were found in both obese (body mass index > = 30 kg/m2) hypertensive and non-obese (body mass index <30 kg/m2) hypertensive patients. Moreover, there was no difference with the blood pressure lowering or adverse effects with regards to the combination therapy in both subgroups.Conclusion:We found that aliskiren/amlodipine combination therapy provided a more effective blood pressure reduction than monotherapy with either drug without increase in the occurrence of adverse events. © 2013 Liu et al.

Yue R.,Chongqing Medical University | Yue R.,Chongqing Institute of Cardiology | Xia X.,Chongqing Medical University | Xia X.,Chongqing Institute of Cardiology | And 16 more authors.
Journal of Cellular Physiology | Year: 2015

Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)-injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R-injury is unclear. In the present study, we aimed to determine if and how lycopene protects cardiomyocytes from I/R-injury. In both in vitro and in vivo studies, I/R-injury increased mt 8-hydroxyguanine (8-OHdG) content, decreased mtDNA content and mtDNA transcription levels, and caused mitochondrial dysfunction in cardiomyocytes. These effects of I/R injury on cardiomycoytes were blocked by pre-treatment with lycopene. MtDNA depletion alone was sufficient to induce cardiomyocyte death. I/R-injury decreased the protein level of a key activator of mt transcription, mitochondrial transcription factor A (Tfam), which was blocked by lycopene. The protective effect of lycopene on mtDNA was associated with a reduction in mitochondrial ROS production and stabilization of Tfam. In conclusion, lycopene protects cardiomyocytes from the oxidative damage of mtDNA induced by I/R-injury. © 2015 Wiley Periodicals, Inc.

Yang Y.,Chongqing Medical University | Yang Y.,Chongqing Institute of Cardiology | Cai Y.,Chongqing Medical University | Cai Y.,Chongqing Institute of Cardiology | And 18 more authors.
Clinical Science | Year: 2015

Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of cardiovascular disease (CVD), but whether circulating lncRNAs can serve as a coronary artery disease (CAD), biomarker is not known. The present study screened lncRNAs by microarray analysis in the plasma from CAD patients and control individuals and found that 265 lncRNAs were differentially expressed. To find specific lncRNAs as possible CAD biomarker candidates, we used the following criteria for 174 up-regulated lncRNAs: signal intensity ≥8, fold change > 2.5 and P < 0.005. According to these criteria, five intergenic lncRNAs were identified. After validation by quantitative PCR (qPCR), one lncRNA was excluded from the candidate list. The remaining four lncRNAs were independently validated in another population of 20 CAD patients and 20 control individuals. Receiver operating characteristic (ROC) curve analysis showed that lncRNA AC100865.1 (referred to as CoroMarker) was the best of these lncRNAs. CoroMarker levels were also stable in plasma. The predictive value of CoroMarker was further assessed in a larger cohort with 221 CAD patients and 187 control individuals. Using a diagnostic model with Fisher's criteria, taking the risk factors into account, the optimal sensitivity of CoroMarker for CAD increased from 68.29% to 78.05 %, whereas the specificity decreased slightly from 91.89% to 86.49 %. CoroMarker was stable in plasma because it was mainly in the extracellular vesicles (EVs), probably from monocytes. We conclude that CoroMarker is a stable, sensitive and specific biomarker for CAD. © 2015 Authors.

Loading Chongqing Institute of Cardiology collaborators
Loading Chongqing Institute of Cardiology collaborators