BackgroundTissue remodeling is usually dependent on the deposition of extracellular matrix that may result in tissue stiffness and impaired myocardium contraction.ObjectivesWe had previously demonstrated that renal ischemia/reperfusion (I/R) is able to induce development of cardiac hypertrophy in mice. Therefore, we aimed to characterize renal I/R-induced cardiac hypertrophy.DesignC57BL/6 J mice were subjected to 60 minutes’ unilateral renal pedicle occlusion, followed by reperfusion (I/R) for 5, 8, 12 or 15 days. Gene expression, protein abundance and morphometric analyses were performed in all time points.ResultsLeft ventricle wall thickening was increased after eight days of reperfusion (p < 0.05). An increase in the number of heart ventricle capillaries and diameter after 12 days of reperfusion (p < 0.05) was observed; an increase in the density of capillaries starting at 5 days of reperfusion (p < 0.05) was also observed. Analyses of MMP2 protein levels showed an increase at 15 days compared to sham (p < 0.05). Moreover, TGF-β gene expression was downregulated at 12 days as well TIMP 1 and 2 (p < 0.05). The Fourier-transform infrared spectroscopy analysis showed that collagen content was altered only in the internal section of the heart (p < 0.05); such data were supported by collagen mRNA levels.ConclusionsRenal I/R leads to impactful changes in heart morphology, accompanied by an increase in microvasculature. Although it is clear that I/R is able to induce cardiac remodeling, such morphological changes is present in only a section of the heart tissue.

ObjectivesNowadays, some studies has emphasize the apoptosis plays a decisive role in cardiac hypertrophy. The aim of this study was to investigate if apoptotic factors were altered in heart after renal ischemia/reperfusion.MethodsC57bl/6J mice were subjected to unilateral 60 min kidney ischemia, followed by reperfusion of 5, 8, 12, 15 and 20 days. Levels of urea were measured to confirm renal failure and gene expression were analyzed by real time PCR.ResultsUrea levels were increased in groups 5, 15 and 20 days (P<0.05). The group 15 days showed a significant increase in heart weight/body weight ratio when compared to sham group. The AIF was increased at 8 and 12 days groups (P<0.05), whereas the anti‐apoptotic Bcl‐2 mRNA levels were increased after 8 days (P<0.05). The Caspase 3 and 9 mRNA levels were increased only after 15 days of reperfusion (p<0.05).ConclusionFirst, the results indicate that renal ischemia/reperfusion model is able to induce a transient cardiac hypertrophy in mice. Levels of mRNA analysis suggests that pro‐apoptotic AIF, Bid, Caspase 3 and 9 might be involved to modulation of cardiac hypertrophy, since we observed an increase in major pro‐apoptotic factors at the same time we observed an increase in cardiac mass.

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.