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GW27-e1014 c-Met overexpression promote reendothelialization and inhibit neointimal formation after balloon injury
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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
nuclear translocation of b-catenin. Inhibition of GSK3b activity significantly accelerated the network formation of EPCs in ApoE-/mice.
administered to evaluate reendothelialization after 10 days injury, and the neointimal formation was assessed at 21 days following vascular injury.
CONCLUSIONS Inhibition of GSK 3b activity not only augment EPCs survival and function partly by increasing expression of downstream molecules but also affected EPCs microenvironment by paracrine effect. Inhibition of GSK 3b activity not only augment EPCs survival and function partly by increasing expression of downstream molecules but also affected EPCs microenvironment by paracrine effect.
RESULTS The effect of HGF on EPC proliferation was examined 48 h after exposure to different quantities of HGF (range 2-20 ng/ml). The proliferation effect was strongly dose-dependent and significantly increased in c-met-EPCs group compared with EPCs group. After transfusion of c-met-EPCs or EPCs to balloon-injured rat via vessel, Evans Blue dye was administered to evaluate reendothelialization after balloon injury. reendothelialized area was significantly larger in c-met-EPCs group than in EPCs group(64.258.90% vs. 43.217.24%, n¼5, P<0.01). A marked decrease in the neointimal area and I/M ratio was found in c-met-EPCs compared with EPCs group at day 21(0.290.06 vs. 0.630.13, n¼5, P<0.01).
GW27-e1006 TUDCA Attenuates Intermittent Hypoxia-Induced MMP-9 Protein Expression in Macrophage Yunyun Yang, Yanwen Qin Beijing An Zhen Hospital, Capital Medical University OBJECTIVES Obstructive sleep apnea syndrome (OSAS) is a clinic syndrome characters with repeated apnea, intermittent hypoxia, frequent arousals during sleeping at night whether companied with hypercapnia or not. Studies suggest that OSAS is being considered as an independent risk factor for cardiovascular diseases, leading to increased multi-morbidity and mortality. Chronic intermittent hypoxia is the most important feature of OSAHS. Chronic intermittent hypoxia promoted the formation of atherosclerosis and plaque rupture, however its mechanism is not yet clear. Matrix metalloproteinases (MMPs) and cysteine protease (Cathepsins) participates in the formation of atherosclerosis through promoting inflammation and extracellular matrix degradation. Endoplasmic reticulum stress signaling pathway participates in the development of atherosclerosis formation. To observe the role of endoplasmic reticulum stress in chronic intermittent hypoxia induced protease expression in macrophage. METHODS Human macrophages cells (THP-1) were exposed to chronic intermittent hypoxia (2%w21% FiO2 60min/cycle) respectively 24h, 48h, 72h. The cells were divided into three groups: control group, chronic intermittent hypoxia group, chronic intermittent hypoxia and endoplasmic reticulum stress inhibitors (TUDCA) group in different doses (2.5uL and 5uL, 500umol/L). Cells morphological changes were detected by optical microscope. Cells viability was detected by MTT. The expression of endoplasmic reticulum stress related protein glucose-regulated protein 78 (GRP78), protein kinaselike ER kinase (PERK), phosphorylation eukaryotic initiation factor 2 alpha (P-EIF2 alpha), activating transcription factor 4 (ATF4), and the expression of MMP-9 and Cathepsis S level were detect by Western Blot. RESULTS Chronic intermittent hypoxia increased the expression of MMP-9 and cathepsin S significantly compared with control group in a time-dependent manner (p < 0.05). Chronic intermittent hypoxia also increased GRP78, PERK, P-EIF2 alpha and ATF4 expression in 48h and 72h significantly compared with control group (p < 0.05). TUDCA (5 uL) group abolished chronic intermittent hypoxia induced MMP-9 protein expression significantly (p < 0.05). TUDCA (5 uL) group significant inhibited the expression of P-EIF2 alpha (p < 0.05). CONCLUSIONS Chronic intermittent hypoxia promoted the protein expression of MMP-9, Cathepsin S and endoplasmic reticulum stress related protein expression in THP-1 cells. TUDCA inhibited the expression of MMP-9 induced by chronic intermittent hypoxia in THP1 cells may through endoplasmic reticulum stress pathway. This may provide a new target for the prevention and treatment of atherosclerosis combined with OSAS. GW27-e1014 c-Met overexpression promote reendothelialization and inhibit neointimal formation after balloon injury Song Mingbao, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES to explore the effect of c-met overexpression in EPCs on reendothelialization after balloon injury. METHODS EPCs derived from mouse bone marrow were isolated and cultured. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were used to evaluate EPC proliferation. Adenoviral vector expressing c-Met was generated using the AdEasy system. To evaluate the role of HGF/Met in vascular repair in vivo, we used balloon-injured rat carotid artery model. Evans Blue dye was
CONCLUSIONS c-Met overexpression improve EPCs proliferation, promote reendothelialization and inhibit neointimal formation after balloon injury. GW27-e1020 The relationship of the genetic polymorphism of ApoE and the stability of carotid plaque Zhang Bo, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES The aim of the present study was to investigate the role of genetic polymorphisms of ApoE in carotid artery atherosclerosis and the instability of the plaque. METHODS 238 subjects were divided into 3 groups: the instable plaque group, stable plaque group and control group according to the result of carotid ultrasound examination. The genetype of ApoE and serum ApoE concentration was measured. The relationship between the genetic polymorphism of ApoE and the instability of carotid plaque was studied with linear and logistic regression analysis. RESULTS ①The frequency of ε4 allele in the CAS subjects was higher than the health people. It was higher in instable plaque group than the stable plaque, and this was statistically significant. ②The average of IMT of the subjects with ε4 allele was 1.22mm, which was significant thicker than the subjects without ε4 allele.。③The ApoE ε4 allele is an independent relative factor of the instable plaque when age, sex and blood fat were adiusted in logistic regression analysis. ④The level of Hs-CRP and MCP-1 in serum of the subjects with allele ε4 were higher than the subjects without it, which indicated that the inflammatory activity in subjects with ε4 allele was stronger than the subjects without ε4 allele. CONCLUSIONS ApoE polymorphism was associated with carotid atherosclerosis and the instability of plaques. Patients with the ApoE4 isoform had a more severe CAS than the subjects without the ApoE e4 allele. Thegenetic polymorphism of ApoE has influenced the arteriosclerosis through adjusting the blood-fat or the chronic inflammation status. GW27-e1023 Atorvastain Attenuates TNF-a-induced Increase of Glucose Oxidation Through PGC-1a Upregulation in cardiomyocytes Wang Jiang, Shanjun Zhu The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES Recent studies have shown that atorvastain has antiinflammatory effect and can prevent cardiac hypertrophy. The development of cardiac hypertrophy and dysfunction is associated with an increase in cardiac glucose utilization. METHODS In this study, we investigated the effect of atorvastatin on glucose oxidation in tumour necrosis factor-a (TNF-a)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor co-activator -1a (PGC-1a) in this effect. RESULTS Exposure of H9c2 cells to TNF-a inhibited the expressions of PGC-1a, pyruvate dehydrogenase kinase 4 (PDK4), carnitine palmityl transferase 1 (CPT1) and induced a significant increase in glucose oxidation rate. However, these effects of TNF-a were significantly reversed by atorvastatin. Selective silence of PGC-1a in H9c2 cells resulted in the down-regulation of PDK4 and CPT1 and further increased the TNF-a-induced glucose oxidation. Interestingly, the
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
nuclear translocation of b-catenin. Inhibition of GSK3b activity significantly accelerated the network formation of EPCs in ApoE-/mice.
administered to evaluate reendothelialization after 10 days injury, and the neointimal formation was assessed at 21 days following vascular injury.
CONCLUSIONS Inhibition of GSK 3b activity not only augment EPCs survival and function partly by increasing expression of downstream molecules but also affected EPCs microenvironment by paracrine effect. Inhibition of GSK 3b activity not only augment EPCs survival and function partly by increasing expression of downstream molecules but also affected EPCs microenvironment by paracrine effect.
RESULTS The effect of HGF on EPC proliferation was examined 48 h after exposure to different quantities of HGF (range 2-20 ng/ml). The proliferation effect was strongly dose-dependent and significantly increased in c-met-EPCs group compared with EPCs group. After transfusion of c-met-EPCs or EPCs to balloon-injured rat via vessel, Evans Blue dye was administered to evaluate reendothelialization after balloon injury. reendothelialized area was significantly larger in c-met-EPCs group than in EPCs group(64.258.90% vs. 43.217.24%, n¼5, P<0.01). A marked decrease in the neointimal area and I/M ratio was found in c-met-EPCs compared with EPCs group at day 21(0.290.06 vs. 0.630.13, n¼5, P<0.01).
GW27-e1006 TUDCA Attenuates Intermittent Hypoxia-Induced MMP-9 Protein Expression in Macrophage Yunyun Yang, Yanwen Qin Beijing An Zhen Hospital, Capital Medical University OBJECTIVES Obstructive sleep apnea syndrome (OSAS) is a clinic syndrome characters with repeated apnea, intermittent hypoxia, frequent arousals during sleeping at night whether companied with hypercapnia or not. Studies suggest that OSAS is being considered as an independent risk factor for cardiovascular diseases, leading to increased multi-morbidity and mortality. Chronic intermittent hypoxia is the most important feature of OSAHS. Chronic intermittent hypoxia promoted the formation of atherosclerosis and plaque rupture, however its mechanism is not yet clear. Matrix metalloproteinases (MMPs) and cysteine protease (Cathepsins) participates in the formation of atherosclerosis through promoting inflammation and extracellular matrix degradation. Endoplasmic reticulum stress signaling pathway participates in the development of atherosclerosis formation. To observe the role of endoplasmic reticulum stress in chronic intermittent hypoxia induced protease expression in macrophage. METHODS Human macrophages cells (THP-1) were exposed to chronic intermittent hypoxia (2%w21% FiO2 60min/cycle) respectively 24h, 48h, 72h. The cells were divided into three groups: control group, chronic intermittent hypoxia group, chronic intermittent hypoxia and endoplasmic reticulum stress inhibitors (TUDCA) group in different doses (2.5uL and 5uL, 500umol/L). Cells morphological changes were detected by optical microscope. Cells viability was detected by MTT. The expression of endoplasmic reticulum stress related protein glucose-regulated protein 78 (GRP78), protein kinaselike ER kinase (PERK), phosphorylation eukaryotic initiation factor 2 alpha (P-EIF2 alpha), activating transcription factor 4 (ATF4), and the expression of MMP-9 and Cathepsis S level were detect by Western Blot. RESULTS Chronic intermittent hypoxia increased the expression of MMP-9 and cathepsin S significantly compared with control group in a time-dependent manner (p < 0.05). Chronic intermittent hypoxia also increased GRP78, PERK, P-EIF2 alpha and ATF4 expression in 48h and 72h significantly compared with control group (p < 0.05). TUDCA (5 uL) group abolished chronic intermittent hypoxia induced MMP-9 protein expression significantly (p < 0.05). TUDCA (5 uL) group significant inhibited the expression of P-EIF2 alpha (p < 0.05). CONCLUSIONS Chronic intermittent hypoxia promoted the protein expression of MMP-9, Cathepsin S and endoplasmic reticulum stress related protein expression in THP-1 cells. TUDCA inhibited the expression of MMP-9 induced by chronic intermittent hypoxia in THP1 cells may through endoplasmic reticulum stress pathway. This may provide a new target for the prevention and treatment of atherosclerosis combined with OSAS. GW27-e1014 c-Met overexpression promote reendothelialization and inhibit neointimal formation after balloon injury Song Mingbao, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES to explore the effect of c-met overexpression in EPCs on reendothelialization after balloon injury. METHODS EPCs derived from mouse bone marrow were isolated and cultured. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were used to evaluate EPC proliferation. Adenoviral vector expressing c-Met was generated using the AdEasy system. To evaluate the role of HGF/Met in vascular repair in vivo, we used balloon-injured rat carotid artery model. Evans Blue dye was
CONCLUSIONS c-Met overexpression improve EPCs proliferation, promote reendothelialization and inhibit neointimal formation after balloon injury. GW27-e1020 The relationship of the genetic polymorphism of ApoE and the stability of carotid plaque Zhang Bo, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES The aim of the present study was to investigate the role of genetic polymorphisms of ApoE in carotid artery atherosclerosis and the instability of the plaque. METHODS 238 subjects were divided into 3 groups: the instable plaque group, stable plaque group and control group according to the result of carotid ultrasound examination. The genetype of ApoE and serum ApoE concentration was measured. The relationship between the genetic polymorphism of ApoE and the instability of carotid plaque was studied with linear and logistic regression analysis. RESULTS ①The frequency of ε4 allele in the CAS subjects was higher than the health people. It was higher in instable plaque group than the stable plaque, and this was statistically significant. ②The average of IMT of the subjects with ε4 allele was 1.22mm, which was significant thicker than the subjects without ε4 allele.。③The ApoE ε4 allele is an independent relative factor of the instable plaque when age, sex and blood fat were adiusted in logistic regression analysis. ④The level of Hs-CRP and MCP-1 in serum of the subjects with allele ε4 were higher than the subjects without it, which indicated that the inflammatory activity in subjects with ε4 allele was stronger than the subjects without ε4 allele. CONCLUSIONS ApoE polymorphism was associated with carotid atherosclerosis and the instability of plaques. Patients with the ApoE4 isoform had a more severe CAS than the subjects without the ApoE e4 allele. Thegenetic polymorphism of ApoE has influenced the arteriosclerosis through adjusting the blood-fat or the chronic inflammation status. GW27-e1023 Atorvastain Attenuates TNF-a-induced Increase of Glucose Oxidation Through PGC-1a Upregulation in cardiomyocytes Wang Jiang, Shanjun Zhu The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES Recent studies have shown that atorvastain has antiinflammatory effect and can prevent cardiac hypertrophy. The development of cardiac hypertrophy and dysfunction is associated with an increase in cardiac glucose utilization. METHODS In this study, we investigated the effect of atorvastatin on glucose oxidation in tumour necrosis factor-a (TNF-a)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor co-activator -1a (PGC-1a) in this effect. RESULTS Exposure of H9c2 cells to TNF-a inhibited the expressions of PGC-1a, pyruvate dehydrogenase kinase 4 (PDK4), carnitine palmityl transferase 1 (CPT1) and induced a significant increase in glucose oxidation rate. However, these effects of TNF-a were significantly reversed by atorvastatin. Selective silence of PGC-1a in H9c2 cells resulted in the down-regulation of PDK4 and CPT1 and further increased the TNF-a-induced glucose oxidation. Interestingly, the