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

Abstract

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.

Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction

“…Other cardiac GPCRs with significantly different expression in TAC vs. SHAM rat hearts identified only by ddPCR in the current study were also shown to be involved in the pathogenesis of HF. For instance, the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor type 1 ( Adcyp1r1 ) was previously shown to mediate the detrimental effects of PACAP, a neuropeptide in HF of different etiologies [ 52 , 53 ]. Endothelin and its receptors ( Ednra , Ednrb ) were also previously associated with HF; however, inhibition of endothelin receptors by bosentan failed to improve outcomes of patients with severe chronic HF [ 54 ].…”

Molecular mechanisms for the prevention and promoting the recovery from ischemic stroke by nutraceutical laminarin: A comparative transcriptomic approach

“…In addition to the reported candidates, our results also highlight some novel therapeutic targets to improve the quality of blood vessels for preventing ischemic stroke, such as adenylate cyclase activating polypeptide 1 (ADCYAP1), natriuretic peptide receptor-C (NPR3), and bradykinin receptor B2 (BDKRB2). ADCYAP1 is known as the pituitary adenylate cyclase-activating peptide (PACAP), which is a multifunctional neuropeptide (21). PACAP has been reported to be actively transported across the blood-brain barrier and plays a role in headache disorders, such as migraine (22).…”

Role of endocrine PACAP in age-related diseases

“…Each abovementioned IL showed significant positive correlation to PACAP concentrations in HF cohort. More remarkable positive correlation was detected between these cytokines and plasma PACAP levels taking the type of HF into consideration ( 72 ).…”