PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study.

Dora Szabo,Eva Saghy,Andras Makkos,Attila Gyenesei,Zsuzsanna Helyes,Andrea Tamas,Peter Ferdinandy,Attila Cziraki,Dora Reglodi,Robert Herczeg,Aniko Gorbe,Adam Nemeth,Zsolt Sarszegi,Beata Polgar

doi:10.3390/ijms22062883

Abstract

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.

Highlights

We examined the different echocardiographic parameters related to the myocardial infarction (MI): ejecWe examined the different echocardiographic parameters related to the MI: ejection fraction, left ventricular end-diastolic diameter, the grade of mitral insufficiency and tion fraction, left ventricular end-diastolic diameter, the grade of mitral insufficiency and the number of the affected segments
The nerve fibers are damaged in the ischemic region, we did not measure significantly lower level of Pituitary adenylate cyclase activating polypeptide (PACAP)-38 in the ischemic region of MI-left ventricle (LV) compared to Sham-operated group (Sham) samples
The nerve fibers are damaged in the ischemic region, we detected similar PACAP-38 levels in the ischemic region of MI-LV compared to the Sham-LV heart samples, because the increased PACAP immunoreactivity in the myocytes, macrophages and the extracellular matrix could compensate the decreased PACAP level caused by the nerve injury

Summary

Introduction

Despite modern interventional therapeutic options, acute myocardial infarction (MI). Is still one of the most common causes of cardiovascular mortality and morbidity [1]. Cardiac biomarkers play an important role in the diagnosis of MI. Based on the latest recommendation of the European Society of Cardiology, the elevated high-sensitive cardiac troponin (hs-cTn) level prove the presence of myocardial injury, even though the elevated values do not represent the underlying cardiac or systemic pathologies [2]. The guideline highlights the complexity of the clinical circumstances making the differentiation difficult between ischemic and non-ischemic conditions associated with increased cTn levels [2]

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Methods

Conclusion