Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium

Abstract

Background:The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation (AF). The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the pro-arrhythmic effect of EAT. Methods & Results: EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-hour EAT culture media (n=8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Co-culture with β-adrenergic agonists isoproterenol (n=4) and BRL37344 (n=13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae (n=10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula developed force (maximal 2.9-fold increase, P< 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P= 0.002) and relaxation (1.8-fold increase,P= 0.007). Additionally, the post-rest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca2+-handling. Conclusions: EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behaviour in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect.

Evidence that resistin acts on the mechanical responses of the mouse gastric fundus

“…Several potential resistin receptors have been suggested but its specific one has not yet been identified and scarce information concerning the downstream signaling mechanisms of action is available (Badoer, 2021). Nevertheless, the hormone has been reported to be involved in a broad range of physiological and pathological conditions, both in rodents and in humans, acting centrally and peripherally (Aitken-Buck et al, 2020;Recinella et al, 2020;Deb et al, 2021;Rachwalik et al, 2021). In particular, resistin acting at the hypothalamic level influences energy homeostasis and modulates feeding, displaying anorexigenic effects in rodents (Brunetti et al, 2004;Tovar et al, 2005;Vázquez et al, 2008;Cifani et al, 2009).…”

Antiresistin Neutralizing Antibody Alleviates Doxorubicin-Induced Cardiac Injury in Mice

“…Numerous studies have demonstrated that resistin participates in insulin resistance, diabetes, and CVD [ 6 , 13 , 14 ]. In patients with peripheral artery disease (PAD), a higher level of resistin was associated with worsened endothelial function and an increased risk of major adverse cardiac events [ 13 ].…”