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GW27-e0659 Daxx Inhibit the Proliferation of VSMC Cells via Regulation of PTEN Signaling Pathway
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
GW27-e0615 The Antibody of Recombinant cyclophilin A Attenuate myocardial inflammatory damage of Lipopolysaccharide-induced mice via downregulation of neutrophil extracellular traps formation Liao Jinli, Jia Xu, Yan Xiong, Ren Jiang, Ziyu Zheng, Hong Zhan Department of Emergency, 1st Affiliated hospital of SUN Yat-sen University OBJECTIVES To investigate the contribute of antibody of recombinant cyclophilin A of mouse on reducing neutrophil extracellular traps formation, therefore improving inflammatory injury of myocardium and cardiac function. METHODS Healthy New Zealand rabbit was immunized with 1 mg rMoCyPA protein three times at an interval of two weeks to obtain anti-rMoCyPA serum.Specific IgG values was measured to determine immune response provoked by rMoCyPA. Male Balb/c mice were randomed into 3 groups:Control group,LPS group,LPSþanti-rMoCyPA group.The rMoCyPA-immunized serum was complement-inactivated and injected via caudal vein in recipient rats 2h after LPS administration.72h mortality and cardiac microscopic changes were evaluated.HE staining were used to assess inflammatory damage at different time points.The mRNA expression level of functional tissue factor, IL-8, IL-6 and TNF-a of myocardium were detected by RT-PCR.The NETs were observed by laser confocal microsope.The ventricular function was evaluated in mice by echocardiography. RESULTS Anti-rMoCyPA serum significantly reduced the 72h mortality of septic mice, alleviated the macroscopic and microscopic damages of inflammatory reaction.The functional tissue factor,IL-8, IL-6 and TNF-a mRNA expression level of myocardium were reduced in mice treated by anti-rMoCyPA serum compared with LPS group and control group.Less NETs were observed with anti-rMoCyPA intervention combined with improved state of myocardial dysfunction,characterized by increased LV ejection fraction. CONCLUSIONS Through down-regulating NETs formation, anti-rMoCyPA serum could alleviated inflammatory injury of myocardial tissues and restore LV function in LPS-induced septic mice. GW27-e0638 Study on the protection effect and mechanism of DB on myocardial ischemia Zhang Yi,1,2 Pengfei Tu1 1 Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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especially through COX2. DBE also can up-regulate the expression of proteins in JAK-STAT pathway, including p-JAK2, and p-STAT3, which has been found as the key pathway of inflammatory and oxidative stress. mTOR pathway also was activated by DBE through up-regulating the P-S6 protein, thereby activating the expression of VEGF, HIF-1a and PPARg proteins in mTOR pathway. Besides, the Western Blot results also showed that DB can inhibit fibrosis mediated by TGF-b. CONCLUSIONS DBE has definite cardiac protective efficacy in improving cardiac function mainly mediated by down-regulating the COX2, JAK-STAT pathway, TGF-b-smad pathway and up-regulating the mTOR pathway. These findings provide strong evidence for cardiac protective efficacy of DBE and validate the beneficial effects of DBE in the clinical application for myocardial ischemia. GW27-e0659 Daxx Inhibit the Proliferation of VSMC Cells via Regulation of PTEN Signaling Pathway Qiu Fei, Dongmei Yang, Qinhui Tuo Hunnan University of Chinese Medicine OBJECTIVES The abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is an important factor of vascular pathologies, such as atherosclerosis and restenosis. The study of Daxx on the regulation of VSMCs was in favor of revealing new drug targets, providing a theoretical basis for the prevention of atherosclerosis. METHODS Firstly, we were used the lipsomal transfections take the plasmid of pCDNA3.1(þ), pCDNA3.1- Daxx(þ) into VSMCs to established the stable cell lines.the expression of Daxx were detected by RT- PCR and western blotting respectively. MTT and flow cytometry were respectively used to determine cellular vitality and cell cycle. Cell migration was detected by scratch wound assay. RT-PCR and western bloting were used to detect the expression of PTEN mRNA and some protein, respectively. RESULTS VSMCs treated with PDGF 20ng/ml for 24h, the cell viability, the sphase of cell cycle and the migration of VSMCs were significantly increased and the expression of Daxx protein was decreased. After transfected the Daxx gene in VSMCs, the cell viability, the sphase of cell cycle and the migration of VSMCs induced by PDGF were significantly decreased, But the shRNA-Daxx was plays an opposite role in it.Furthermore,Daxx could up-regulation the expression of PTEN gene and protein, down-regulation the expression of NF-kBp65 and p-Akt protein. When we silented PTEN gene in the Daxx gene-transfected VSMC, the cell proliferation and migration were significantly increased, which also increased the activation of NF-kB and Akt
OBJECTIVES Dragon’s Blood (DB), a Chinese traditional herb, was validated to have definite protective effects on activating circulation to remove blood stasis. More evidence demonstrated that DB has a dramatic efficacy on treating acute myocardial infarction (AMI). However, governing mechanism of its therapeutic effects remains unclear. This study is to reveal the underlying mechanism of the antimyocardial ischemia effect of DB extract (DBE).
CONCLUSIONS Daxx inhibits the VSMC proliferation might though the PTEN/Akt/NF-kB signaling pathway.
METHODS C57 mice were randomly divided into 5 groups: sham group, model group, DBE groups (with 600mg/kg dose and 300mg/ kg dose respectively), and aspirin group. After pre- therapeutic administration for 7 days, the mice were subjected to left anterior descending (LAD) artery ligation. While in sham group, needle was only passed around the artery without ligation. 24 hours after surgery, heart function was evaluated by 2D echocardiography. CK-MB and LDH in serum, TXB2 and 6-keto-PGF1a in plasma were detected. Protein expressions of COX-1, COX-2, p-JAK2, p-STAT3, VEGF, P-S6, TGF-b and PPARg were measured by western-blot.
Dongming Hou,2 Jeannot Potvin,1 Elena Ladich,3 Barbara Huibregtse,2 Renu Virmani,3 Keith Dawkins,2 Amelie Bouchard,4 Guy Leclerc4 1 Centre Hospitalier de I’Universite de Montreal; 2BSC; 3CVPath; 4 AccelLAB
RESULTS Echocardiography results showed that EF and FS significantly decreased in model group compared to sham group. An increase in values of LVEDd and LVESd was also observed in the model group, suggesting that myocardial ischemia was successfully induced. In DBE treated group, EF and FS were significantly up-regulated compared with those in the model group. In addition, DBE could decrease CK-MB and LDH obviously compared with model group. Moreover, the DBE can also up-regulate 6-keto-PGF1 a and downregulate TXB2 so as to keep balance between 6-keto-PGF1a and TXB2 compared with the model group and be closer to the sham group when compared to aspirin group. Different doses of DBE can reduce apoptosis mediated by different subtypes of cyclooxygenases,
GW27-e0696 Hemodynamic and Biology Response of a Fully Repositionable and Retrievable TAVI System in a Sheep Model
OBJECTIVES The present study is aimed to 1) determine the feasibility of transfemoral orthotopic transcatheter aortic valve implantation, and 2) evaluate the in vivo hemodynamic and healing response of the Lotus? device in a sheep model. METHODS A total of 17 adolescent sheep were pre-screened by CT with a proper aortic anatomy to use the fully repositionable and retrievable 27mm Lotus? valve system, and enrolled in the study. Under intra-cardiac echocardiography (ICE) and fluoroscopic guidance, Lotus valve placement was attempted in all animals, of which 14 survived the TAVI procedures. There was a total of five unscheduled deaths, all of which occurred intra or peri-procedurally. Three were due to ventricular fibrillation (VF) which followed complete AV block (n¼2) or right coronary obstruction (n¼1). The other two deaths occurred during recovery: VF of unknown cause (n¼1) and ventricular embolization of the implanted device (n¼1). Therefore, twleve animals survived to planned termination points at 90d (n¼2) and 140d (n¼10).
GW27-e0615 The Antibody of Recombinant cyclophilin A Attenuate myocardial inflammatory damage of Lipopolysaccharide-induced mice via downregulation of neutrophil extracellular traps formation Liao Jinli, Jia Xu, Yan Xiong, Ren Jiang, Ziyu Zheng, Hong Zhan Department of Emergency, 1st Affiliated hospital of SUN Yat-sen University OBJECTIVES To investigate the contribute of antibody of recombinant cyclophilin A of mouse on reducing neutrophil extracellular traps formation, therefore improving inflammatory injury of myocardium and cardiac function. METHODS Healthy New Zealand rabbit was immunized with 1 mg rMoCyPA protein three times at an interval of two weeks to obtain anti-rMoCyPA serum.Specific IgG values was measured to determine immune response provoked by rMoCyPA. Male Balb/c mice were randomed into 3 groups:Control group,LPS group,LPSþanti-rMoCyPA group.The rMoCyPA-immunized serum was complement-inactivated and injected via caudal vein in recipient rats 2h after LPS administration.72h mortality and cardiac microscopic changes were evaluated.HE staining were used to assess inflammatory damage at different time points.The mRNA expression level of functional tissue factor, IL-8, IL-6 and TNF-a of myocardium were detected by RT-PCR.The NETs were observed by laser confocal microsope.The ventricular function was evaluated in mice by echocardiography. RESULTS Anti-rMoCyPA serum significantly reduced the 72h mortality of septic mice, alleviated the macroscopic and microscopic damages of inflammatory reaction.The functional tissue factor,IL-8, IL-6 and TNF-a mRNA expression level of myocardium were reduced in mice treated by anti-rMoCyPA serum compared with LPS group and control group.Less NETs were observed with anti-rMoCyPA intervention combined with improved state of myocardial dysfunction,characterized by increased LV ejection fraction. CONCLUSIONS Through down-regulating NETs formation, anti-rMoCyPA serum could alleviated inflammatory injury of myocardial tissues and restore LV function in LPS-induced septic mice. GW27-e0638 Study on the protection effect and mechanism of DB on myocardial ischemia Zhang Yi,1,2 Pengfei Tu1 1 Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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especially through COX2. DBE also can up-regulate the expression of proteins in JAK-STAT pathway, including p-JAK2, and p-STAT3, which has been found as the key pathway of inflammatory and oxidative stress. mTOR pathway also was activated by DBE through up-regulating the P-S6 protein, thereby activating the expression of VEGF, HIF-1a and PPARg proteins in mTOR pathway. Besides, the Western Blot results also showed that DB can inhibit fibrosis mediated by TGF-b. CONCLUSIONS DBE has definite cardiac protective efficacy in improving cardiac function mainly mediated by down-regulating the COX2, JAK-STAT pathway, TGF-b-smad pathway and up-regulating the mTOR pathway. These findings provide strong evidence for cardiac protective efficacy of DBE and validate the beneficial effects of DBE in the clinical application for myocardial ischemia. GW27-e0659 Daxx Inhibit the Proliferation of VSMC Cells via Regulation of PTEN Signaling Pathway Qiu Fei, Dongmei Yang, Qinhui Tuo Hunnan University of Chinese Medicine OBJECTIVES The abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is an important factor of vascular pathologies, such as atherosclerosis and restenosis. The study of Daxx on the regulation of VSMCs was in favor of revealing new drug targets, providing a theoretical basis for the prevention of atherosclerosis. METHODS Firstly, we were used the lipsomal transfections take the plasmid of pCDNA3.1(þ), pCDNA3.1- Daxx(þ) into VSMCs to established the stable cell lines.the expression of Daxx were detected by RT- PCR and western blotting respectively. MTT and flow cytometry were respectively used to determine cellular vitality and cell cycle. Cell migration was detected by scratch wound assay. RT-PCR and western bloting were used to detect the expression of PTEN mRNA and some protein, respectively. RESULTS VSMCs treated with PDGF 20ng/ml for 24h, the cell viability, the sphase of cell cycle and the migration of VSMCs were significantly increased and the expression of Daxx protein was decreased. After transfected the Daxx gene in VSMCs, the cell viability, the sphase of cell cycle and the migration of VSMCs induced by PDGF were significantly decreased, But the shRNA-Daxx was plays an opposite role in it.Furthermore,Daxx could up-regulation the expression of PTEN gene and protein, down-regulation the expression of NF-kBp65 and p-Akt protein. When we silented PTEN gene in the Daxx gene-transfected VSMC, the cell proliferation and migration were significantly increased, which also increased the activation of NF-kB and Akt
OBJECTIVES Dragon’s Blood (DB), a Chinese traditional herb, was validated to have definite protective effects on activating circulation to remove blood stasis. More evidence demonstrated that DB has a dramatic efficacy on treating acute myocardial infarction (AMI). However, governing mechanism of its therapeutic effects remains unclear. This study is to reveal the underlying mechanism of the antimyocardial ischemia effect of DB extract (DBE).
CONCLUSIONS Daxx inhibits the VSMC proliferation might though the PTEN/Akt/NF-kB signaling pathway.
METHODS C57 mice were randomly divided into 5 groups: sham group, model group, DBE groups (with 600mg/kg dose and 300mg/ kg dose respectively), and aspirin group. After pre- therapeutic administration for 7 days, the mice were subjected to left anterior descending (LAD) artery ligation. While in sham group, needle was only passed around the artery without ligation. 24 hours after surgery, heart function was evaluated by 2D echocardiography. CK-MB and LDH in serum, TXB2 and 6-keto-PGF1a in plasma were detected. Protein expressions of COX-1, COX-2, p-JAK2, p-STAT3, VEGF, P-S6, TGF-b and PPARg were measured by western-blot.
Dongming Hou,2 Jeannot Potvin,1 Elena Ladich,3 Barbara Huibregtse,2 Renu Virmani,3 Keith Dawkins,2 Amelie Bouchard,4 Guy Leclerc4 1 Centre Hospitalier de I’Universite de Montreal; 2BSC; 3CVPath; 4 AccelLAB
RESULTS Echocardiography results showed that EF and FS significantly decreased in model group compared to sham group. An increase in values of LVEDd and LVESd was also observed in the model group, suggesting that myocardial ischemia was successfully induced. In DBE treated group, EF and FS were significantly up-regulated compared with those in the model group. In addition, DBE could decrease CK-MB and LDH obviously compared with model group. Moreover, the DBE can also up-regulate 6-keto-PGF1 a and downregulate TXB2 so as to keep balance between 6-keto-PGF1a and TXB2 compared with the model group and be closer to the sham group when compared to aspirin group. Different doses of DBE can reduce apoptosis mediated by different subtypes of cyclooxygenases,
GW27-e0696 Hemodynamic and Biology Response of a Fully Repositionable and Retrievable TAVI System in a Sheep Model
OBJECTIVES The present study is aimed to 1) determine the feasibility of transfemoral orthotopic transcatheter aortic valve implantation, and 2) evaluate the in vivo hemodynamic and healing response of the Lotus? device in a sheep model. METHODS A total of 17 adolescent sheep were pre-screened by CT with a proper aortic anatomy to use the fully repositionable and retrievable 27mm Lotus? valve system, and enrolled in the study. Under intra-cardiac echocardiography (ICE) and fluoroscopic guidance, Lotus valve placement was attempted in all animals, of which 14 survived the TAVI procedures. There was a total of five unscheduled deaths, all of which occurred intra or peri-procedurally. Three were due to ventricular fibrillation (VF) which followed complete AV block (n¼2) or right coronary obstruction (n¼1). The other two deaths occurred during recovery: VF of unknown cause (n¼1) and ventricular embolization of the implanted device (n¼1). Therefore, twleve animals survived to planned termination points at 90d (n¼2) and 140d (n¼10).