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GW27-e0442 The protective effect of Huoluoxiaoling Dan on the apoptosis of endothelial cell induced by H2O2
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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
it decreased from (86.815.92) % to (72.859.80) % in a descending manner. SEM indicated that the surface of NFBS developed a tight arrangement of endothelial cells with complete coverage in 6 months. Stereoscopic observations revealed the stent struts could retain a clear shape in 1 month; and reduce uneven thickness with indistinct edges and progressed corrosion-like changes in 12 months. CONCLUSIONS The lumen of PLLA/ACP scaffold increased with the growth of reference vessel in 24 months. Late positive remodeling and late lumen gain can be archived in NFBS-treated vessels, which contributes to vascular restoration due to scaffold degradation and unattainable in the DES-caged segments. These benefits demonstrated preclinically may translate into improvements in long-term clinical outcomes for patients treated with NFBS compared with DES. GW27-e0439 Cdkn1a Knockout Alleviates Pressure Overload Induced Cardiac Remodeling Man Xu, Qizhu Tang Department of cardiology, Renmin Hospital of Wuhan university, Wuhan, Hubei Province, China OBJECTIVES One novel contributor to maladaptive cardiac remodeling is excessive myocytes hypertrophic growth, during which mitogens and other stimuli activate cell cycle proteins and their specific inhibitors.Cdkn1a is an important member of the cyclin-dependent kinase inhibitor (CDKI) family, which plays a crucial regulative role in cell-cycle progression. It has been known that myocardial Cdkn1a is up regulated under stimuli, the intracellular signaling mechanisms underlying its effect remain poorly understood. Present study was to investigate a novel role of Cdkn1a in the regulation of pressure overload induced cardiac remodeling. METHODS Mice with global deletion of Cdkn1a (Cdkn1a-/-) and their wild type (WT) littermates were subjected to chronic pressure overload via aortic banding (AB) or sham surgery. Cardiac function was assessed via echocardiogram and pulmonary hemodynamics 4 weeks post-operation. Left ventricular tissue was excised for testing of the hypertrophic magnitude, interstitial collagen volume, transcriptome variations and alterations in protein signaling pathways. Neonatal rat cardiomyocytes (NRCMs) transfected with ShDNA plasmid of pSi-Cdkn1a targeting Cdkn1a mRNA was primary cultured and stimulated with angiotensin II (Ang II) for further verification in vitro. RESULTS The up-regulated expression of Cdkn1 a was observed after AB. Heart weight/body weight (HW/BW), parameters of left ventricular contractility, relaxation and compliance function showed that Cdkn1a-/- mice have limited myocyte hypertrophy, reduced fibrosis and preserved heart function compared with WT mice. Cdkn1a-/- mice revealed restricted expression of AB-forced pro-inflammatory cytokines and pro-apoptotic proteins. Phosphorylation in PI3K/AKT/ FoxO3a signaling pathway was down-regulated in Cdkn1a-/- mice, and hence the abundance of FoxO3a nuclear translocation and the level of its downstream anti-apoptotic protein ARC was increased. Consistent with the in vivo results, with the downregulation of Cdkn1a by pSi-Cdkn1a, NRCMs were prevented from Ang II induced hypertrophy and apoptosis. CONCLUSIONS Cdkn1a knockout protects the heart from pressure overload induced cardiac remodeling through PI3K/AKT/FoxO3a pathway.
RESULTS Hydrogen peroxide could decrease the activity of endothelial cells in a dose-dependent manner, and induce apoptosis. Among them, after 500 mmol/L H2O2, cell proliferation was obviously inhibited, and the content of caspase-3, caspase-9 and GRP78, XBP1were significantly increased(P<0.01).After the addition of Huoluoxiaoling Dan, the survival rate of cells increased, and compared with the H2O2 model, 80ug/ml of Huoluoxiaoling Dan pretreatment could significantly inhibit apoptosis, and decreased the expression of caspase-3, caspase-9 and GRP78, XBP1 (P<0.01). CONCLUSIONS Huoluoxiaoling Dan can inhibit the apoptosis of endothelial cells induced by hydrogen peroxide, which may be related to the down-regulation of the endoplasmic reticulum stress related proteins. GW27-e0447 Effect of hypertonic sodium chloride hydroxyethyl starch 40 on expression of MMP-9 and Laminin after rats cerebral ischemia reperfusion injury Shan Reai1,3 1 Department of Anesthesiology, First Affiliated Hospital of Gannan Medical University; 3Institute of pain medicine, Gannan medical university OBJECTIVES To observe the effect of Hypertonic Sodium Chloride Hydroxyethyl Starch 40 (HSH) on neurological deficits scores, degree of encephaledema, cerebral infarction volume andexpression of MMP-9 and Laminin in a rat model of ischemia/reperfusion(I/R) injury. METHODS 48 male SD rats were randomly divided into four groups: shamed-operation group (group A), model group (group B), HSH 4ml/ kg group (group C) and HSH 8ml/kg group (group D). Rat focal cerebral I/R injury model was simulated by middle cerebral artery occlusion (MCAO). 120 minutes after modeling, group A, B were treated with physiological saline and group C, D were treated with HSH by sublingual vein injection. 24 hours after reperfusion, nerve function was evaluated by using Longa’s score-line in every rat, six of every group’sdegree of encephaledema would be observed and TTC staining would be applied to measure the cerebral infarction volume after taking out the brain. Expression of MMP-9 and Laminin were detected with western blotting in ischemic penumbra of the other six after observing the degree of encephaledema. RESULTS The percentage of cerebral infarction volume and neurological behavioral score of group B was more than these of group A(p<0.001)with an obviousencephaledema. The expression of MMP-9 of group B significantly increased versus group A (p<0.05),but Laminin decreased (p<0.05). Compared with group B,The percentage of cerebral infarction volume and neurological behavioral score of group C, D dereased (p<0.001)with a catabatic degree of encephaledema. The expression of MMP-9 of group C significantly decreased versus group B(p<0.05), but Laminin increased (p<0.05). Group D had no obvious change. CONCLUSIONS MMP-9 protein would be more activated and accelerate the degradation of Laminin protein so that BBB’s permeability increased on rat cerebral I/R. Meanwhile, encephaledema and cerebral infarction happened and neurological behavioral score increased. HSHcan significantly reduce BBB’s permeability, cerebral infarct volume, degree of encephaledema and neurological dysfunction in rat I/R injury models. These findings indicated that MMP-9 and Laminin may be involved in the protective mechanisms of HSHagainst cerebral ischemia/reperfusion injury. According to the dose of HSH, 4 ml/kg is better than 8 ml/kg.
GW27-e0442 The protective effect of Huoluoxiaoling Dan on the apoptosis of endothelial cell induced by H2O2
GW27-e0505 Echocardiography-guided percutaneous per-apical laser ablation of ovine ventricular septum — mid-term effects
Lizhen Hao, Xingzhou Gao, Hong Chang, Houwang Jiang, Xinlou Chai Beijing University of Chinese Medicine
Sun Chao, Jianli Fu, Guangbin He, Rui Hu, Fang Liu, Ruiqi Guo, Chuang Ye, Jianguo He, Liwen Liu, Liu liwen Xijing Hospital, Fourth Military Medical University
OBJECTIVES To study the effect of Huoluoxiaoling Dan on the apoptosis of human umbilical vein endothelial cells in vitro induced by hydrogen peroxide (H2O2), and to explore the mechanism. METHODS Human umbilical vein endothelial cells were cultured in vitro, Huoluoxiaoling Dan water solution pretreated the cells for 24h, and then used the H2O2 on HUVECs for 4h. MTT was used to detect the growth activity of the cells, and flow cytometry was used to detect the apoptosis rate, the protein GRP78, XBP1, caspase-3 and caspase-9 were detected by Western blot.
OBJECTIVES Currently surgical myectomy and ethanol ablation are two established interventions for relieving the left ventricular outflow obstruction in obstructive hypertrophic cardiomyopathy (HOCM) patients. The limitations in safety and efficacy in these interventions call for minimally invasive, potentially safer and more efficacious approach. Our previous study showed that echocardiography-guided percutaneous per-ventricular laser ablation of canine ventricular septum was effective and safe in short-term. However,
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
it decreased from (86.815.92) % to (72.859.80) % in a descending manner. SEM indicated that the surface of NFBS developed a tight arrangement of endothelial cells with complete coverage in 6 months. Stereoscopic observations revealed the stent struts could retain a clear shape in 1 month; and reduce uneven thickness with indistinct edges and progressed corrosion-like changes in 12 months. CONCLUSIONS The lumen of PLLA/ACP scaffold increased with the growth of reference vessel in 24 months. Late positive remodeling and late lumen gain can be archived in NFBS-treated vessels, which contributes to vascular restoration due to scaffold degradation and unattainable in the DES-caged segments. These benefits demonstrated preclinically may translate into improvements in long-term clinical outcomes for patients treated with NFBS compared with DES. GW27-e0439 Cdkn1a Knockout Alleviates Pressure Overload Induced Cardiac Remodeling Man Xu, Qizhu Tang Department of cardiology, Renmin Hospital of Wuhan university, Wuhan, Hubei Province, China OBJECTIVES One novel contributor to maladaptive cardiac remodeling is excessive myocytes hypertrophic growth, during which mitogens and other stimuli activate cell cycle proteins and their specific inhibitors.Cdkn1a is an important member of the cyclin-dependent kinase inhibitor (CDKI) family, which plays a crucial regulative role in cell-cycle progression. It has been known that myocardial Cdkn1a is up regulated under stimuli, the intracellular signaling mechanisms underlying its effect remain poorly understood. Present study was to investigate a novel role of Cdkn1a in the regulation of pressure overload induced cardiac remodeling. METHODS Mice with global deletion of Cdkn1a (Cdkn1a-/-) and their wild type (WT) littermates were subjected to chronic pressure overload via aortic banding (AB) or sham surgery. Cardiac function was assessed via echocardiogram and pulmonary hemodynamics 4 weeks post-operation. Left ventricular tissue was excised for testing of the hypertrophic magnitude, interstitial collagen volume, transcriptome variations and alterations in protein signaling pathways. Neonatal rat cardiomyocytes (NRCMs) transfected with ShDNA plasmid of pSi-Cdkn1a targeting Cdkn1a mRNA was primary cultured and stimulated with angiotensin II (Ang II) for further verification in vitro. RESULTS The up-regulated expression of Cdkn1 a was observed after AB. Heart weight/body weight (HW/BW), parameters of left ventricular contractility, relaxation and compliance function showed that Cdkn1a-/- mice have limited myocyte hypertrophy, reduced fibrosis and preserved heart function compared with WT mice. Cdkn1a-/- mice revealed restricted expression of AB-forced pro-inflammatory cytokines and pro-apoptotic proteins. Phosphorylation in PI3K/AKT/ FoxO3a signaling pathway was down-regulated in Cdkn1a-/- mice, and hence the abundance of FoxO3a nuclear translocation and the level of its downstream anti-apoptotic protein ARC was increased. Consistent with the in vivo results, with the downregulation of Cdkn1a by pSi-Cdkn1a, NRCMs were prevented from Ang II induced hypertrophy and apoptosis. CONCLUSIONS Cdkn1a knockout protects the heart from pressure overload induced cardiac remodeling through PI3K/AKT/FoxO3a pathway.
RESULTS Hydrogen peroxide could decrease the activity of endothelial cells in a dose-dependent manner, and induce apoptosis. Among them, after 500 mmol/L H2O2, cell proliferation was obviously inhibited, and the content of caspase-3, caspase-9 and GRP78, XBP1were significantly increased(P<0.01).After the addition of Huoluoxiaoling Dan, the survival rate of cells increased, and compared with the H2O2 model, 80ug/ml of Huoluoxiaoling Dan pretreatment could significantly inhibit apoptosis, and decreased the expression of caspase-3, caspase-9 and GRP78, XBP1 (P<0.01). CONCLUSIONS Huoluoxiaoling Dan can inhibit the apoptosis of endothelial cells induced by hydrogen peroxide, which may be related to the down-regulation of the endoplasmic reticulum stress related proteins. GW27-e0447 Effect of hypertonic sodium chloride hydroxyethyl starch 40 on expression of MMP-9 and Laminin after rats cerebral ischemia reperfusion injury Shan Reai1,3 1 Department of Anesthesiology, First Affiliated Hospital of Gannan Medical University; 3Institute of pain medicine, Gannan medical university OBJECTIVES To observe the effect of Hypertonic Sodium Chloride Hydroxyethyl Starch 40 (HSH) on neurological deficits scores, degree of encephaledema, cerebral infarction volume andexpression of MMP-9 and Laminin in a rat model of ischemia/reperfusion(I/R) injury. METHODS 48 male SD rats were randomly divided into four groups: shamed-operation group (group A), model group (group B), HSH 4ml/ kg group (group C) and HSH 8ml/kg group (group D). Rat focal cerebral I/R injury model was simulated by middle cerebral artery occlusion (MCAO). 120 minutes after modeling, group A, B were treated with physiological saline and group C, D were treated with HSH by sublingual vein injection. 24 hours after reperfusion, nerve function was evaluated by using Longa’s score-line in every rat, six of every group’sdegree of encephaledema would be observed and TTC staining would be applied to measure the cerebral infarction volume after taking out the brain. Expression of MMP-9 and Laminin were detected with western blotting in ischemic penumbra of the other six after observing the degree of encephaledema. RESULTS The percentage of cerebral infarction volume and neurological behavioral score of group B was more than these of group A(p<0.001)with an obviousencephaledema. The expression of MMP-9 of group B significantly increased versus group A (p<0.05),but Laminin decreased (p<0.05). Compared with group B,The percentage of cerebral infarction volume and neurological behavioral score of group C, D dereased (p<0.001)with a catabatic degree of encephaledema. The expression of MMP-9 of group C significantly decreased versus group B(p<0.05), but Laminin increased (p<0.05). Group D had no obvious change. CONCLUSIONS MMP-9 protein would be more activated and accelerate the degradation of Laminin protein so that BBB’s permeability increased on rat cerebral I/R. Meanwhile, encephaledema and cerebral infarction happened and neurological behavioral score increased. HSHcan significantly reduce BBB’s permeability, cerebral infarct volume, degree of encephaledema and neurological dysfunction in rat I/R injury models. These findings indicated that MMP-9 and Laminin may be involved in the protective mechanisms of HSHagainst cerebral ischemia/reperfusion injury. According to the dose of HSH, 4 ml/kg is better than 8 ml/kg.
GW27-e0442 The protective effect of Huoluoxiaoling Dan on the apoptosis of endothelial cell induced by H2O2
GW27-e0505 Echocardiography-guided percutaneous per-apical laser ablation of ovine ventricular septum — mid-term effects
Lizhen Hao, Xingzhou Gao, Hong Chang, Houwang Jiang, Xinlou Chai Beijing University of Chinese Medicine
Sun Chao, Jianli Fu, Guangbin He, Rui Hu, Fang Liu, Ruiqi Guo, Chuang Ye, Jianguo He, Liwen Liu, Liu liwen Xijing Hospital, Fourth Military Medical University
OBJECTIVES To study the effect of Huoluoxiaoling Dan on the apoptosis of human umbilical vein endothelial cells in vitro induced by hydrogen peroxide (H2O2), and to explore the mechanism. METHODS Human umbilical vein endothelial cells were cultured in vitro, Huoluoxiaoling Dan water solution pretreated the cells for 24h, and then used the H2O2 on HUVECs for 4h. MTT was used to detect the growth activity of the cells, and flow cytometry was used to detect the apoptosis rate, the protein GRP78, XBP1, caspase-3 and caspase-9 were detected by Western blot.
OBJECTIVES Currently surgical myectomy and ethanol ablation are two established interventions for relieving the left ventricular outflow obstruction in obstructive hypertrophic cardiomyopathy (HOCM) patients. The limitations in safety and efficacy in these interventions call for minimally invasive, potentially safer and more efficacious approach. Our previous study showed that echocardiography-guided percutaneous per-ventricular laser ablation of canine ventricular septum was effective and safe in short-term. However,