背景:急性心肌梗死(AMI)是全球范围内心脏性猝死的主要原因。可以改善AMI风险预测的新生物标志物的发现满足了对高风险患者的识别和药物治疗的定制的主要临床需求。以前,我们报道自噬是一种高度保守的细胞内降解细胞成分的分解代谢机制,涉及动脉粥样硬化斑块表型和心脏病理重构。自噬在正常和患病心脏中的关键作用已经得到了很好的描述,它的激活作用是响应心肌缺血的促生存过程。然而,自噬在缺血/再灌注损伤中失调,从而促进坏死或凋亡的心肌细胞死亡。很少有研究关注心血管疾病患者的自噬标志物的血浆水平,即使它们可能是AMI损伤的伴随生物标志物。本研究的目的是评估:1)两个关键自噬调节因子ATG5(自噬相关基因5)和Beclin1(哺乳动物酵母直系同源物Atg6/Vps30)的血浆水平变化是否与AMI和2有关)它们预测AMI风险的潜力。
方法:病例对照研究人群包括心血管风险高但无已知冠心病的AMI患者(n=100)和对照组(n=99)。通过酶联免疫吸附测定在整个人群研究中测量ATG5和Beclin1的血浆水平。
结果:多变量分析根据常见的心血管因素和药物治疗进行调整,和受试者工作特征(ROC)曲线表明:ATG5和Beclin1水平与AMI呈负相关,并为AMI风险预测提供了原始生物标志物。
结论:自噬调节因子ATG5和Beclin1的血浆水平代表与AMI相关的候选生物标志物。
BACKGROUND: Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk.
METHODS: The
case-control study population included AMI patients (n = 100) and control subjects (n = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay.
RESULTS: Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction.
CONCLUSIONS: Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.