Hypoxia‐inducible factor‐1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin‐1 expression correlates with angiogenesis in congenital heart disease
Hypoxia‐inducible factor‐1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin‐1 expression correlates with angiogenesis in congenital heart disease
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DOI：
10.1016/j.kjms.2016.05.011
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
H. Yin;C. Luo;Z. Dai;K. Shaw;C. Chai;Chun-Chieh Wu
中科院分区：
文献类型：
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作者：
H. Yin;C. Luo;Z. Dai;K. Shaw;C. Chai;Chun-Chieh Wu
在台湾，先天性心脏病(CHD)的平均患病率为13.08/1000活产儿。大多数CHD儿童在5岁之前死亡；因此，确定延长CHD患者生命的治疗方法是临床实践中的一个重要问题。本研究的目的是探讨低氧诱导因子-1α、血管内皮生长因子、诱导型一氧化氮合酶、内皮素-1和CD34在冠心病尸检中的作用，并与非冠心病尸检病例进行比较。尸检病例19例，分为4组：先天性心脏病组11例，青紫型冠心病组3例，合并染色体异常组3例，复杂型冠心病组2例。以10例非冠心病尸检的心脏标本为对照。结果表明，在冠心病尸检标本中，缺氧诱导因子-1α(100%)、血管内皮生长因子(89.5%)、诱导型一氧化氮合酶(78.9%)和内毒素-1(84.2%)的表达均较高，且差异有统计学意义。缺氧诱导的缺氧诱导因子-1α可能与冠心病者下游基因的表达有关。缺氧诱导因子-1α上调血管内皮细胞生长因子可能在低氧微环境下启动血管生成保护心肌细胞存活中发挥重要作用。因此，低氧诱导因子-1α可作为冠心病预后的重要指标，有望成为心血管疾病靶向治疗的候选靶点。
In Taiwan, the average prevalence of congenital heart disease (CHD) is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n= 11), cyanotic CHD (n= 3), CHD associated with chromosomal abnormalities (n= 3), and complex CHD (n= 2). Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%), VEGF (89.5%), iNOS (78.9%), and ET-1 (84.2%) expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.