Apelin protects against sepsis-induced cardiomyopathy by inhibiting the TLR4 and NLRP3 signaling pathways

Abstract

The mechanism underlying sepsis-induced cardiomyopathy (SICM) remains unclear. The aim of the present study was therefore to illuminate the mechanisms and effects of apelin on SICM, using both patient clinical features and a sepsis rat model. A total of 73 adult patients with or without sepsis were analyzed. Male rats were used to generate the sepsis model through cecal ligation and puncture (CLP). The clinical analysis results demonstrated that sepsis induced cardiac dysfunction, including a decrease of left ventricular end-diastolic dimension, fractional shortening, ejection fraction, left ventricular end-systolic dimension, and stroke volume, compared with healthy controls. In addition, the results demonstrated that white blood cell count and inflammatory cytokine expression increased in sepsis patients compared with healthy controls. ELISA analyses revealed that apelin was upregulated following sepsis. The animal model study demonstrated that rats treated with apelin had significantly reduced mortality and suppressed sepsis-induced myocardial damage and inflammatory responses, through suppression of activation of the Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3) signaling pathways. Taken together, the present results suggested that apelin had a protective effect against sepsis-induced cardiac impairment by attenuating TLR4 and NLRP3 signaling-mediated inflammatory responses.