Knockout of Toll‐like Receptors 2 and 4 Prevents Renal Ischemia‐Reperfusion‐Induced Cardiac Hypertrophy

Abstract

BackgroundIt is known that renal ischemia reperfusion (I/R) generates a systemic inflammatory state, promoting molecular and morphological changes in the heart tissue, but the mechanisms remain unknown. TLRs are largely studied in the heart and are known to participate of inflammatory process, moreover it has been demonstrated their role in cardiac hypertrophy (CH) development.AimThe aim of this study was to investigate whether cardiac TLRs pathways are involved in renal I/R‐induced CH.Methods/ResultsC57BL/6J, TLR2‐/‐ and TLR4‐/‐ mice were subjected to unilateral 60 min renal ischemia followed by reperfusion for 5, 8, 12 and 15 days. A serum peak of inflammatory cytokines was observed after 5 days of reperfusion. Heart weight/tibia length (HW/TL) ratio was increased after 12 days of reperfusion, as well as CH markers BNP and alpha‐actin. Cardiac electrical activity showed longer QT, QTc and action potential duration after 15 days. Cardiac TLRs, NF‐kB, MyD88, HSP60 and 70 mRNA levels were increased in the 15‐days group. After 15 days of reperfusion, the absence of TLRs prevented CH development, as reflected by similar values of HW/TL compared to transgenic non‐ischemic mice, as well as lower expression of HSP and NF‐kB, suggesting that renal IR‐induced increase of these molecules was prevented.ConclusionsThese results indicate that (i) TLRs play a key role on renal IR‐induced CH; (ii) prevention of hypertrophic response was independent of renal function recovery; (iii) TLR2 and TLR4 selectively regulate the systemic inflammatory profile.