急性冠脉综合征患者中可溶性血管内皮生长因子受体异构体的血浆水平、循环蝶呤及血管内皮生长因子系统单核苷酸多态性作为预后生物标志物
Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes.
作者信息
Marks Edward C A, Wilkinson Tom M, Frampton Chris M, Skelton Lorraine, Pilbrow Anna P, Yandle Tim G, Pemberton Chris J, Doughty Robert N, Whalley Gillian A, Ellis Chris J, Troughton Richard W, Owen Maurice C, Pattinson Neil R, Cameron Vicky A, Richards A Mark, Gieseg Steven P, Palmer Barry R
机构信息
Christchurch Heart institute, Department of Medicine, University of Otago, PO Box 4345, Christchurch, New Zealand.
School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
出版信息
BMC Cardiovasc Disord. 2018 Aug 15;18(1):169. doi: 10.1186/s12872-018-0894-1.
BACKGROUND
Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2.
METHODS
Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042).
RESULTS
At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027).
CONCLUSIONS
sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.
背景
冠状动脉疾病中侧支循环的形成具有心脏保护作用。形成新血管的一个关键过程是单核细胞被吸引到闭塞动脉，随后被激活成为巨噬细胞。在一个前瞻性招募的急性冠状动脉综合征队列的患者中，我们研究了三种活化巨噬细胞产物、可溶性血管内皮生长因子（VEGF）受体（sFlt-1和sKDR）和蝶呤，以及VEGF受体基因VEGFR-1和VEGFR-2中的基因变异的预后性能。
方法
在冠状动脉疾病队列研究（CDCS，n = 2067）的亚组（分别为n = 513；211；144）的血浆样本中测量sFlt-1（VEGFR1）、sKDR（VEGFR2）和蝶呤的基线水平。对该队列的DNA样本进行基因分型，检测VEGFR-1基因单核苷酸多态性（rs748252，n = 2027；rs9513070，n = 2048）和VEGFR-2基因单核苷酸多态性（rs2071559，n = 2050；rs2305948，n = 2066；rs1870377，n = 2042）。
结果
在基线时，sFlt-1水平与年龄、饮酒量、NTproBNP、BNP以及其他与心血管病理生理学相关的协变量显著相关。总蝶呤水平与基线时的饮酒量相关。7,8-二氢新蝶呤与体重指数相关。VEGFR-2变异rs1870377的A等位基因与基线时较高的血浆sFlt-1水平和较低的sKDR水平相关。基线血浆sFlt-1与全因死亡率单因素相关（p < 0.001），在Cox比例风险回归模型中，sFlt-1和蝶呤均与死亡率相关，且独立于已确定的预测因素（p < 0.027）。
结论
sFlt-1和蝶呤可能有潜力作为急性冠状动脉综合征患者的预后生物标志物。VEGF系统基因的遗传标记作为这些患者VEGF系统成分水平的标记值得进一步研究。
试验注册
澳大利亚新西兰临床试验注册中心。ACTRN12605000431628。2005年9月16日，回顾性注册。
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