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.

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.

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson’s disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson’s disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

Endurance training-induced changes in left ventricular diastolic function and right ventricular parameters have been investigated extensively in adolescent athletes. Our aim was to examine the parameters for adolescent athletes (n=121, 15.1±1.6 years) compared to adult athletes and age-matched non-athletes. We explored the effects of influencing factors on the echocardiographic parameters. Significantly higher E/A (p<0.05) and e’ values (p<0.001) were detected in adolescent athletes compared to age-matched non-athletes’ and also adult athletes’ parameters. Significantly lower structural and functional right ventricular parameters (p<0.05) were detected in adult athletes. In adolescent athletes significantly higher right ventricular diameters, tricuspid S wave, right ventricular end-diastolic and end-systolic area values (p<0.05) were found compared to the matching parameters of non-athletes. We found significantly higher corrected tricuspid annular plane systolic excursion values (p<0.001) in athletes compared to the non-athletes. Based on multivariate analysis lean body mass, body surface area, age and cumulative training time were proved as strong predictive factors of both left ventricular diastolic and right ventricular parameters. Supernormal left ventricular diastolic function and significantly higher right ventricular parameters are indicative of cardiac adaptation. Well-defined cut-off values should be applied to discriminate pathological conditions in the relation of the influencing factors.

Background: Exercise-induced left ventricular hypertrophy (LVH) has been extensively investigated in adolescent athletes using the conventional two-tiered classification (2TC). However, the four-tiered classification (4TC) allows further differentiation of LVH patterns by incorporating three-dimensional information on left ventricular (LV) geometry. This study aimed to compare LVH assessment using the two classification systems and characterize the reclassification patterns. Methods: A total of 121 adolescent athletes (mean age: 15.1 ± 1.6 years) and 114 adult athletes (mean age: 22.9 ± 3.7 years), all competing at the national level, underwent comprehensive echocardiographic and anthropometric evaluations. Results: The application of 4TC resulted in redistribution across LV geometric categories compared with conventional 2TC. Twenty-three (19.0%) adolescent and 25 (22%) adult athletes were reclassified, including seven (5.8%) and 17 (15%), respectively, who shifted from normal geometry under the 2TC to different LVH categories under the 4TC. Reclassification was observed across sex and sporting discipline subgroups, although the patterns varied. In runners and triathletes, the combined prevalence of eccentric non-dilated and eccentric dilated LVH was 22.7% using the 4TC versus 4.5% eccentric LVH under the 2TC classification. LVM was strongly associated with the combined contribution of cumulative training duration, lean body mass, and body surface area (r = 0.785, p < 0.001), whereas training duration alone was not significantly associated with the LVH parameters. Conclusions: The 2TC and 4TC approaches result in different assessments of LV geometry in highly trained athletes, with the 4TC providing additional characterization of LVH patterns by considering the presence or absence of LV dilatation. Reclassification patterns varied according to sex and sporting discipline, highlighting the importance of sport-related characteristics when interpreting exercise-induced LV remodeling in athletes.