PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients

Int J Mol Sci. 2022 Mar 28;23(7):3715. doi: 10.3390/ijms23073715.


Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.

Keywords: NT-proBNP; cytokines; heart failure; ischemic/non-ischemic cardiomyopathy; pituitary adenylate cyclase activating polypeptide.

MeSH terms

  • Heart Failure*
  • Humans
  • Myocardium / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide* / metabolism
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism


  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I