急性冠脉综合征患者HIF-1α、VEGF及ET-1水平的临床意义
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摘要
目的:
通过对冠心病急性冠脉综合征(ACS)患者和冠心病稳定型心绞痛患者(SAP)血清缺氧诱导因子- 1α(H IF - 1α)、血管内皮生长因子(VEGF)和内皮素-1(ET-1)浓度的检测来探讨:1)ACS患者血清HIF-1α、VEGF和ET-1与临床斑块稳定性的关系;2)寻求在此过程中HIF-1α与VEGF、ET-1之间的相关性;3)评价它们与冠心病患者发生MACE危险性的关系。
方法:
选择急性冠脉综合征患者(ACS组)59例,其中急性心肌梗死(AMI)患者24例,不稳定型心绞痛(UAP)患者35例;稳定型心绞痛患者(SAP)28例;另设对照组33例。所有入选对象均经临床症状和冠脉造影术等确诊,同时使用7-TIMI积分作为发生MACE危险性的定量指标。采用酶联免疫吸附法( ELISA法)测定所血清有入选对象血清H IF - 1α与VEGF水平,用放射免疫法测定血清ET-1水平。应用SPSS13.0版统计软件进行分析,主要统计学指标进行正态检验和方差齐性检验,各统计数据均以(x±S)表示;两两比较采用方差分析,组间比较采用SNK-q检验;相关性分析采用线性相关性分析。双侧p<0.05为差异有统计学意义。
结果:
1.ACS组HIF-1α、VEGF和ET-1水平明显高于SAP组和对照组[ ( 102.3±20.8) ng/ml、( 192.3±32.7) ng/ml、( 80.1±15.9) ng/ml和( 41.5±21.4) ng/ml、( 121.0±22.3)ng/ml、( 45.1±13.3) ng/ml和( 38.1±17.5) ng/ml、( 85.8±19.6) ng/ml、( 32.7±8.9) ng/ml](P<0.05);
2.SAP组HIF-1α水平与对照组比较差异无统计学意义(P>0.05),而VEGF和ET-1水平明显高于对照组(P<0.05);
3.ACS组中AMI亚组HIF-1α、VEGF和ET-1水平明显高于UAP亚组[ ( 127.6±23.4) ng/ml、( 231.5±39.2) ng/ml、( 92.3±17.4) ng/ml和( 90.2±18.7) ng/ml、( 162.4±27.1)ng/ml、( 71.5±14.8) ng/ml](P<0.05);
4.HIF-1α、VEGF和ET-1之间有显著地正相关性(r值分别为0.758及0.675、P 5.血清HIF-1α、VEGF和ET-1水平和7-TIMI危险积分具有正的相关性(r值分别为0.803、0.714及0.762, P 结论:
1.ACS患者血清HIF - 1α、VEGF和ET-1水平明显增高,并可能是ACS患者斑块不稳定性的标志。
2. HIF-1α与VEGF、ET-1之间均具有良好相关关系。
3.血清HIF - 1α、VEGF和、ET-1和7-TIMI危险积分具有正的相关性,说明它们可以成为评价主要心血管恶性事件危险性的相关指标。
Objective:
We detected the serum level of hypoxia - inducible factor - 1α(H IF - 1α)、vascular endothelial growth factor(VEGF) and Endothelin-1(ET-1) in the patients with acute coronary syndrome(ACS) and stable angina pectoris, to find their relationship with the following facters:①their relationship with the stablebility of plaque in clinical studies;②their relationship of HIF-1α、VEGF and ET-1 in the expression of coronary atherosclerosis;③their relationship with the risk of MACE.
Methods:
The patients were chosen and divided into two group:acute coronary syndrome (ACS)group of 59 cases,stable angina pectoris (SAP)group of 28 cases.And the patient with ACS were divided into two sub groups: acute myocardial infarction (AMI) group (24 cases), unstable angina pectoris(UAP) group (35 cases). In addition,33 healthy cases were chosen as control group.Each subject was taken Coronary Artery Angiogram.Using 7-TIMI risk score as the quantitable indexes of the risk of MACE corresponding. The serum level of HIF-1α/VEGF were detected by ELISA and ET-1 detected by RIA in all the cases. Statistical evaluation was performed with 13.0 software.Before statistical evaluation,the normality and the homogeneity of variance of statistical data should be tested,Data were expressed as Mean±SD and compared by ANOVA,Differences among groups were analyzed by SNK-qtest,Correlation analysis was used by linear correlation analysis.Two-side P<0.05 was considered statistically significance.
Results:
1. The levels of HIF-1α/VEGFand ET-1 in ACS group were significantly higher than those in SAP and control groups [ ( 102.3±20.8) ng/ml、( 192.3±32.7) ng/ml、( 80.1±15.9) ng/ml and ( 41.5±21.4) ng/ml、( 121.0±22.3)ng/ml、( 45.1±13.3) ng/ml and ( 38.1±17.5) ng/ml、( 85.8±19.6) ng/ml、( 32.7±8.9) ng/ml] (P <0.05).
2. There was no difference in HIF - 1αbetween SAP and control group (P >0.05), but VEGFand ET-1 in SAP group were higher than those in control group (P <0.05).
3. The levels of HIF-1α、VEGF and ET-1 in AMI sub group were more than that of UAP sub group [ ( 127.6±23.4) ng/ml、( 231.5±39.2) ng/ml、( 92.3±17.4) ng/ml and ( 90.2±18.7) ng/ml、( 162.4±27.1)ng/ml、( 71.5±14.8) ng/ml] (P <0.05).
4. There was a good relationship between HIF-1αand VEGF、HIF-1αand ET-1 during paticipating in coronary atherosclerosis;
5. The risk score7-TIMI for subsequent cardiovascular events were increased in patients with higher serum level of MCP-1 and VEGF.
Conclusions:
1. The more severe ACS was, the higher level of serum HIF-1α、VEGF and ET-1 were. The elevation of HIF-1α、VEGF and ET-1 may be a sign of atherosclerotic plaque destabilization.
2. The serum level of HIF- 1αwere positive correlated with that of VEGF and ET-1.
3. The serum level of HIF-1α、VEGF and ET-1 were positive correlated with 7-TIMI risk score, It prompt that HIF-1α、VEGF and ET-1 was the reactiveness markers of coronary artery process.
通过对冠心病急性冠脉综合征(ACS)患者和冠心病稳定型心绞痛患者(SAP)血清缺氧诱导因子- 1α(H IF - 1α)、血管内皮生长因子(VEGF)和内皮素-1(ET-1)浓度的检测来探讨:1)ACS患者血清HIF-1α、VEGF和ET-1与临床斑块稳定性的关系;2)寻求在此过程中HIF-1α与VEGF、ET-1之间的相关性;3)评价它们与冠心病患者发生MACE危险性的关系。
方法:
选择急性冠脉综合征患者(ACS组)59例,其中急性心肌梗死(AMI)患者24例,不稳定型心绞痛(UAP)患者35例;稳定型心绞痛患者(SAP)28例;另设对照组33例。所有入选对象均经临床症状和冠脉造影术等确诊,同时使用7-TIMI积分作为发生MACE危险性的定量指标。采用酶联免疫吸附法( ELISA法)测定所血清有入选对象血清H IF - 1α与VEGF水平,用放射免疫法测定血清ET-1水平。应用SPSS13.0版统计软件进行分析,主要统计学指标进行正态检验和方差齐性检验,各统计数据均以(x±S)表示;两两比较采用方差分析,组间比较采用SNK-q检验;相关性分析采用线性相关性分析。双侧p<0.05为差异有统计学意义。
结果:
1.ACS组HIF-1α、VEGF和ET-1水平明显高于SAP组和对照组[ ( 102.3±20.8) ng/ml、( 192.3±32.7) ng/ml、( 80.1±15.9) ng/ml和( 41.5±21.4) ng/ml、( 121.0±22.3)ng/ml、( 45.1±13.3) ng/ml和( 38.1±17.5) ng/ml、( 85.8±19.6) ng/ml、( 32.7±8.9) ng/ml](P<0.05);
2.SAP组HIF-1α水平与对照组比较差异无统计学意义(P>0.05),而VEGF和ET-1水平明显高于对照组(P<0.05);
3.ACS组中AMI亚组HIF-1α、VEGF和ET-1水平明显高于UAP亚组[ ( 127.6±23.4) ng/ml、( 231.5±39.2) ng/ml、( 92.3±17.4) ng/ml和( 90.2±18.7) ng/ml、( 162.4±27.1)ng/ml、( 71.5±14.8) ng/ml](P<0.05);
4.HIF-1α、VEGF和ET-1之间有显著地正相关性(r值分别为0.758及0.675、P
1.ACS患者血清HIF - 1α、VEGF和ET-1水平明显增高,并可能是ACS患者斑块不稳定性的标志。
2. HIF-1α与VEGF、ET-1之间均具有良好相关关系。
3.血清HIF - 1α、VEGF和、ET-1和7-TIMI危险积分具有正的相关性,说明它们可以成为评价主要心血管恶性事件危险性的相关指标。
Objective:
We detected the serum level of hypoxia - inducible factor - 1α(H IF - 1α)、vascular endothelial growth factor(VEGF) and Endothelin-1(ET-1) in the patients with acute coronary syndrome(ACS) and stable angina pectoris, to find their relationship with the following facters:①their relationship with the stablebility of plaque in clinical studies;②their relationship of HIF-1α、VEGF and ET-1 in the expression of coronary atherosclerosis;③their relationship with the risk of MACE.
Methods:
The patients were chosen and divided into two group:acute coronary syndrome (ACS)group of 59 cases,stable angina pectoris (SAP)group of 28 cases.And the patient with ACS were divided into two sub groups: acute myocardial infarction (AMI) group (24 cases), unstable angina pectoris(UAP) group (35 cases). In addition,33 healthy cases were chosen as control group.Each subject was taken Coronary Artery Angiogram.Using 7-TIMI risk score as the quantitable indexes of the risk of MACE corresponding. The serum level of HIF-1α/VEGF were detected by ELISA and ET-1 detected by RIA in all the cases. Statistical evaluation was performed with 13.0 software.Before statistical evaluation,the normality and the homogeneity of variance of statistical data should be tested,Data were expressed as Mean±SD and compared by ANOVA,Differences among groups were analyzed by SNK-qtest,Correlation analysis was used by linear correlation analysis.Two-side P<0.05 was considered statistically significance.
Results:
1. The levels of HIF-1α/VEGFand ET-1 in ACS group were significantly higher than those in SAP and control groups [ ( 102.3±20.8) ng/ml、( 192.3±32.7) ng/ml、( 80.1±15.9) ng/ml and ( 41.5±21.4) ng/ml、( 121.0±22.3)ng/ml、( 45.1±13.3) ng/ml and ( 38.1±17.5) ng/ml、( 85.8±19.6) ng/ml、( 32.7±8.9) ng/ml] (P <0.05).
2. There was no difference in HIF - 1αbetween SAP and control group (P >0.05), but VEGFand ET-1 in SAP group were higher than those in control group (P <0.05).
3. The levels of HIF-1α、VEGF and ET-1 in AMI sub group were more than that of UAP sub group [ ( 127.6±23.4) ng/ml、( 231.5±39.2) ng/ml、( 92.3±17.4) ng/ml and ( 90.2±18.7) ng/ml、( 162.4±27.1)ng/ml、( 71.5±14.8) ng/ml] (P <0.05).
4. There was a good relationship between HIF-1αand VEGF、HIF-1αand ET-1 during paticipating in coronary atherosclerosis;
5. The risk score7-TIMI for subsequent cardiovascular events were increased in patients with higher serum level of MCP-1 and VEGF.
Conclusions:
1. The more severe ACS was, the higher level of serum HIF-1α、VEGF and ET-1 were. The elevation of HIF-1α、VEGF and ET-1 may be a sign of atherosclerotic plaque destabilization.
2. The serum level of HIF- 1αwere positive correlated with that of VEGF and ET-1.
3. The serum level of HIF-1α、VEGF and ET-1 were positive correlated with 7-TIMI risk score, It prompt that HIF-1α、VEGF and ET-1 was the reactiveness markers of coronary artery process.
引文
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[3] LICHTENBERG ES, HILL LJ, HOWE M, et al. 1A randomized comparison of p ropofol and methohexital as general anesthetics for vacuum abortion1[J]. Controception, 2003, 68(3): 211.
[4] Celletti FL, Hilfiker PR, Ghafouri P, et al1 Effect of human recombinant vascular endothelial growth factor 165 on p rogression of atherosclerotic plaque[ J ]. J Am Coll Cardiol, 2001, 37 (8) : 2126 - 2130.
[5] Simonini A, Moscuci M, Muller DW, et a1.IL- 8 is an angiogenic factor in human coronary atheretonry tissue. Circulation,2000, 101: 1, 519- 526.
[6] Myszka W.Endothelin-1 in coronary artery disease[J]. PolMerkuriusz -lek, 2001; 11(64): 291.
[7] Zouridakis EG, Schwartzman R, Garcia Moll X, etal. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression[J]. Eur Heart J ,2001,22:1578 -1584.
[8] Mitani H, Takimoto M , Bandoh T , et al. Increasesof vascular endothelin converting enzyme activity andendothelin 1 level on atherosclerotic lesions in hyper lipidemic rabbits [J ]. Eur J Pharmacol ,2000,387:313-319.
[9]李建勇、王彬尧等.HIF-1基因治疗促进缺血心肌血管新生的实验研究[J] .中国心血管病研究杂志,2005,3(9):709-711.
[10] Jing Zhang, Liang Ding et al, Collagen-Targeting VascularEndothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction. Circulation, Apr 2009; 119: 1776 - 1784.
[11] Semenza GL.O22 Regulated gene expression:transcription alcontrol of cardiorespiratory physiology by HIF-1.J Appl Physiol,2004,96(3) :1173-1177.
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[7] Zouridakis EG, Schwartzman R, Garcia Moll X, etal. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression[J ]. Eur Heart J ,2001,22:1578 -1584.
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[2]马晓艳、张言镇、周衍菊,急性冠脉综合征患者血清血管内皮生长因子、缺氧诱导因子-1α水平的变化及临床意义。中国心血管病研究,2008,12,921-923.
[3] LICHTENBERG ES, HILL LJ, HOWE M, et al. 1A randomized comparison of p ropofol and methohexital as general anesthetics for vacuum abortion1[J]. Controception, 2003, 68(3): 211.
[4] Celletti FL, Hilfiker PR, Ghafouri P, et al1 Effect of human recombinant vascular endothelial growth factor 165 on p rogression of atherosclerotic plaque[ J ]. J Am Coll Cardiol, 2001, 37 (8) : 2126 - 2130.
[5] Simonini A, Moscuci M, Muller DW, et a1.IL- 8 is an angiogenic factor in human coronary atheretonry tissue. Circulation,2000, 101: 1, 519- 526.
[6] Myszka W.Endothelin-1 in coronary artery disease[J]. PolMerkuriusz -lek, 2001; 11(64): 291.
[7] Zouridakis EG, Schwartzman R, Garcia Moll X, etal. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression[J]. Eur Heart J ,2001,22:1578 -1584.
[8] Mitani H, Takimoto M , Bandoh T , et al. Increasesof vascular endothelin converting enzyme activity andendothelin 1 level on atherosclerotic lesions in hyper lipidemic rabbits [J ]. Eur J Pharmacol ,2000,387:313-319.
[9]李建勇、王彬尧等.HIF-1基因治疗促进缺血心肌血管新生的实验研究[J] .中国心血管病研究杂志,2005,3(9):709-711.
[10] Jing Zhang, Liang Ding et al, Collagen-Targeting VascularEndothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction. Circulation, Apr 2009; 119: 1776 - 1784.
[11] Semenza GL.O22 Regulated gene expression:transcription alcontrol of cardiorespiratory physiology by HIF-1.J Appl Physiol,2004,96(3) :1173-1177.
[12] Epstein AC,Gleadle JM,McNeillLA,etal.C.elegans EGL-9 and mammalian homologs definea family of dioxygenases that regulate HIF by prolylhy droxylation. Cell, 2001,107(1) :43～54。
[13] Tal R,Shaish A,Bangio L, et al. Activation of C-transacti- vationdomain is essential for optimal HIF - 1 alpha mediated transcriptional and angiogenic effect. Microvasc Res,2008,76:1-6.
[14] SM Chen, YG Li, Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease. Coron Artery Dis, May 2008; 19(3): 173-9.
[15] Simonini A, Moscuci M, Muller DW, et a1.IL- 8 is an angiogenicfactor in human coronary atheretonry tissue. Circulation,2000, 101: 1, 519- 526.
[16] D Panutsopulos, E Papalambros, F Sigala, Protein and mRNA expression levels of VEGF-A and TGF-beta1 in different types of human coronary atherosclerotic lesions. Int J Mol Med, Apr 2005; 15(4): 603-10.
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