Examination of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Potential Biomarker in Heart Failure Patients

J Mol Neurosci. 2019 Jul;68(3):368-376. doi: 10.1007/s12031-017-1025-7. Epub 2018 Jan 20.


Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide having neurotrophic, neuroprotective, and general cytoprotective actions in a variety of tissues based on its anti-apoptotic, anti-inflammatory, and antioxidant effects. Several studies have demonstrated its cardioprotective effects in vitro and in various animal models. However, few data are available on the presence of PACAP in human cardiac tissues and its role in the pathomechanism and progression of different cardiac disorders, particularly heart failure. Earlier, our research group has shown PAC1 receptor immunoreactivity in human heart tissue samples and we have found significantly elevated PACAP27- and PACAP38-like immunoreactivity in ischemic cardiac samples compared to valvular abnormalities with radioimmunoassay. In the last few years, numerous studies examined the presence and the changes of PACAP levels in different human tissue samples and biological fluids to show alterations in different physiological and pathological conditions. Therefore, the aim of the present study was to measure the alterations of blood PACAP levels in chronic heart failure caused by primary dilated cardiomyopathy or ischemic cardiomyopathy and to examine the possible relationship between serum levels of PACAP, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and systolic left ventricular function, the most reliable biomarkers of heart failure. In the group of mild heart failure patients, a significant strong negative correlation was detected. Furthermore, in moderate heart failure, we found a significant moderate negative correlation between PACAP and NT-proBNP levels only in ischemic subgroup. Positive correlation was found between serum PACAP level and ejection fraction only in patients with heart failure due to ischemic cardiomyopathy but not in patients with primary dilated cardiomyopathy. In summary, remarkable differences were observed between the ischemic and non-ischemic heart failure suggesting that PACAP might play an important role in the pathomechanism and progression of ischemic heart failure and it might be a potential biomarker of cardiac diseases in the future.

Keywords: Dilated cardiomyopathy; Heart failure; NT-proBNP; PACAP.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cardiomyopathy, Dilated / blood*
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / physiopathology
  • Female
  • Heart Failure / blood*
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Pituitary Adenylate Cyclase-Activating Polypeptide / blood*
  • Protein Precursors / blood
  • Ventricular Function, Left


  • Biomarkers
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Protein Precursors
  • prepro-brain natriuretic peptide
  • Natriuretic Peptide, Brain