Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander?

Abstract

Objective:Galanin, a cotransmitter similar to neuropeptide Y (NPY), aggravates autonomic imbalance in systolic heart failure (HF) by attenuating vagal tonus after burst sympathetic activity. In animal HF models, galanin antagonists have improved cardiac function. To determine whether galanin is a promising therapeutic target in HF, we studied its concentrations in HF patients and evaluated its correlation with NPY, markers of humoral activity such as pro-BNP and copeptin, and echocardiographic parameters of HF severity.Methods:After recording demographic and echocardiographic characteristics of 87 individuals (57 HF patients and 30 control subjects), fasting serum concentrations of galanin, NPY, copeptin, and pro-BNP were determined.Results:Unlike pro-BNP, copeptin, and NPY, which were significantly elevated in HF patients (p<0.001, p<0.001, and p=0.001, respectively), galanin was similar in HF patients and control subjects (p=0.9). NPY correlated with the echocardiographic parameters of HF severity (r=–0.22, p=0.03 for EF; r=0.3, p=0.005 for Tei index of RV; r=–0.23, p=0.03 for TAPSE; and r=0.24, p=0.024 for E/e¢) and pro-BNP (r=0.22, p=0.046). NPY levels were also associated with beta blocker (BB) use, wherein BB significantly decreased NPY in both HF patients and control subjects. Galanin correlated with humoral biomarkers, pro-BNP and copeptin (r=0.39, p<0.001 and r=0.41, p<0.001, respectively). Although current smoking, BB therapy, pro-BNP, copeptin, and body mass index were associated with galanin in univariate analyses, the multiple linear regression model revealed that pro-BNP was the only significant determinant of galanin levels in HF patients.Conclusion:Our findings confirmed the role of NPY in autonomic balance and suggest that galanin is associated with the proadrenergic state, but its role in HF in humans remains unclear.

The Role of Neuropeptide Y in Cardiovascular Health and Disease

“…In two studies which measured NPY levels in heart failure patients post-exercise, one found no significant increase, whilst one found an increase from 50+/−5 to 60+/−6 pmol/l (Maisel et al, 1989 ; Ullman et al, 1994a ). A more recent study has also confirmed higher NPY levels in heart failure patients, which correlated with BNP levels and echocardiographic markers of heart failure severity (Ozkaramanli Gur et al, 2017 ).…”

Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

“…A recent prospective case-control study in the clinical realm showed that unlike pro-BNP, copeptin and NPY, galanin levels were similar among patients with HF patients and control subjects while pro-BNP was the only significant determinant of galanin levels in HF patients[ 236 ]. Authors postulated that galanin most likely has a predominant paracrine modulatory function at the level of peripheral cardiac sympathetic nerves, therefore, its circulating levels in plasma might not reflect the degree of its local involvement in sympathovagal crosstalk.…”

The Effects of Neuropeptide Y Overexpression on the Mouse Model of Doxorubicin-Induced Cardiotoxicity

“…In this study, we asked if NPY has an effect on DOXinduced cardiotoxicity. Previous studies have shown a diverse role for NPY in different types of cardiomyopathies, including an increase in NPY levels and effects on several pathological processes involved also in DOX-induced cardiotoxicity [11,30,[53][54][55][56]. Transgenic NPY overexpression had some effects on DOX-induced toxicity.…”