Poster No. 049 Cardiopreventive influence of Klotho protein on antioxidant and anti-apoptotic mechanisms in heart injured by ischemia/reperfusion

Ischemia/reperfusion injury (IRI) of heart involves activation of oxidative and apoptotic pathways. Klotho protein has potential protective activity since it supports redox balance and metabolic functions of cardiomyocytes. This study aimed to evaluate effect of Klotho protein on oxidative stress and apoptosis in hearts subjected to IRI.

Isolated rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in presence or absence of Klotho protein. Heart mechanical function and factors involved in the activation of insulin-like growth factor 1 receptor (IGFR-1)/phosphoinositide 3-kinase (PI3K) signaling pathway were evaluated.

Infusion supply of Klotho significantly increased (P = 0.001) mechanical function of hearts injured by IRI. IRI caused activation of IGFR-1/PI3K signalling pathway (P = 0.004; P = 0.003), while Klotho suppressed phosphorylation of IGFR-1 (P = 0.208) and PI3K (P = 0.022). Transcriptional activity of forkhead box protein O1 (FOXO1) and FOXO3 was reduced (P = 0.002; P < 0.001) in IRI hearts. Administration of Klotho decreased phosphorylation of FOXO1 (P = 0.587) and FOXO3 (P = 0.027) in IRI + Klotho group, while activity of glutathione peroxidase and superoxide dismutase was increased (P = 0.045; P = 0.006), and level of hydrogen peroxide and lipid peroxidation was slightly decreased (P = 0.502; P = 0.436), as compared to IRI hearts. Klotho protein contributed to reduction in caspase-9 level (P = 0.009) during IRI.

Administration of Klotho resulted in full preservation of heart mechanical function, and suppression of oxidative stress and apoptosis in IRI hearts. Thus, Klotho can be recognized as a novel cardiopreventive agent in ischemic damage.

Ministry of Science and Higher Education in Poland [grant number SUBK.D010.22.035].