Heart Institute, Medical School, University of Pecs, 7624 Pecs, Hungary.
Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, 7624 Pecs, Hungary.
Int J Mol Sci. 2021 Mar 12;22(6):2883. doi: 10.3390/ijms22062883.
Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.
急性心肌梗死(MI)是全球最常见的死亡原因之一。垂体腺苷酸环化酶激活肽(PACAP)是一种心脏保护性神经肽,在心血管系统中表达其受体。我们的研究目的是在转化猪 MI 模型中检查组织 PACAP-38,并在 ST 段抬高型心肌梗死(STEMI)患者中检查血浆 PACAP-38 水平。与 MI-LV 的缺血区和猪 MI 模型中的 Sham 操作 LV 相比,MI 心脏的左心室(LV)非缺血区中检测到的 PACAP-38 水平明显降低。在 STEMI 患者中,与对照组相比,经皮冠状动脉介入治疗(PCI)前的血浆 PACAP-38 水平明显升高,PCI 后降低。发现血浆 PACAP-38 与肌钙蛋白水平之间存在显著负相关。此外,还揭示了血浆 PACAP-38、高血压和 HbA1c 水平之间存在显著影响。这是第一项在猪 MI 模型中显示心脏组织 PACAP 水平和 STEMI 患者血浆 PACAP 水平发生显著变化的研究。这些结果表明,由于其心脏保护作用,PACAP 可能在 MI 中发挥调节作用,并且可能是 MI 的潜在生物标志物或药物靶标。