Poster No. 050 Klotho protein supports mechanical function and prevents MMP-mediated injury of heart during ischemia/reperfusion

The injury of the myocardium during ischemia/reperfusion (IRI) involves metabolic, morphological, and contractile disorders. Klotho is a membrane or soluble anti-aging protein. Recent studies have proven the correlation between Klotho deficiency and the occurrence and development of cardiovascular diseases. The study aimed to evaluate the effect of Klotho protein on hearts subjected to IRI.

Isolated Wistar rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in the presence or absence of Klotho protein. Hemodynamic parameters and the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Κb), nitrate/nitrite, inducible nitric oxide synthase (iNOS), asymmetric dimethylarginine (ADMA), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of MMP type 4 (TIMP-4) were evaluated.

Infusion supply of Klotho during IRI resulted in the recovery of contractile function (P = 0.031) and heart rate (P = 0.02). IRI activated MMP-2 (P = 0.042) and MMP-9 (P = 0.041) in hearts, as compared to aerobic control. Klotho contributed to increase in iNOS level (P = 0.02), and decreased levels of NF-Κb (P = 0.006), ADMA (P = 0.007), nitrate/nitrite (P = 0.022), MMP-2 (P = 0.024) and MMP-9 (P < 0.001), as compared to IRI group.

Klotho protein preserved heart mechanical function and reduced the level of proteolytic enzymes in the heart. Thus, Klotho can be recognized as a novel cardiopreventive/cardioprotective agent in ischemic damage.

This work was supported by the National Science Centre, Poland [grant number 2019/33/N/NZ3/01649].