Klotho alleviates sepsis-associated myocardial inflammation and apoptosis.

Abstract

Klotho (KL) protects against various pathological phenotypes. The present study was designed to investigate the effect of KL on sepsis-associated cardiac dysfunction, and whether KL modulated sepsis-associated cardiac dysfunction via oxidative stress and apoptosis. Experiments were carried out in mice treated with lipopolysaccharide (LPS) to induce the septic model. The expression of KL was reduced in the heart of septic mice induced by LPS administration. The cardiac dysfunction of septic mice was deteriorated after KL KO, and was alleviated by KL upregulation. The inflammatory factors of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 were increased in the heart after LPS treatment, and these increases were further enhanced in KL deficiency mice, and were alleviated in KL overexpressed mice. The apoptosis biomarkers of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) levels were changed in the heart of septic mice, which were exacerbated by KL KO and were ameliorated by KL overexpression. These results indicated that KL involved in the regulation of sepsis-induced cardiac dysfunction via alleviating inflammation and apoptosis. Upregulation KL may be a therapeutic strategy to improve cardiac function in septic patients in the future.