Characterization of Klotho/FGF23 signaling in cardiorenal syndrome‐induced cardiac hypertrophy

Abstract

IntroductionIn diseases that generate an inflammatory situation, such as cardiorenal syndrome, different clinical conditions promote cardiac and renal dysfunction. There are type 3 and 4 which are characterized by renal insults that subject the heart to dysfunctions; Among the changes that renal injury can lead, we can mention the modulation in Klotho levels, a gene that is negatively regulated by fibroblast growth factor 23 (FGF23). The objective of this study is to evaluate the participation of this axis in cardiac hypertrophy induced by renal ischemiaMethodsC57BL/6 male mice were subjected to surgical occlusion of left renal pedicle for 60 min followed by reperfusion in acute term (24, 48 and 72h), short term (for 8 and 15 days) and long term (4,6 and 8 weeks). Total heart RNA was extracted for gene expression of Klotho, FGF23 and hypertrophy markers using real‐time PCR.ResultsThe renal injury was confirmed by decreasing of left kidney weight and urea/creatinine levels starting at the 15th day of reperfusion. Cardiac hypertrophy was confirmed by increased a‐actin levels at day 15 and 4 weeks of renal reperfusion; however, heart weight has maintained increased until the 8th week of reperfusion. Concerning the FGF23/Klotho axis, both genes were modulated during the cardiorenal syndrome type 3. FGF23 gene expression was mostly increased in heart tissue after 8 days of reperfusion, having its peak during the 4th week. In renal tissue, FGF23 did not present a pattern, although it shows a peak in the first 24 hours, in the 8th day and 15th day (the same timepoints which the heart tissue is affect which electrophysiological and immunological changes). By the other side, Klotho gene expression was mostly reduced in renal tissue after 48h of reperfusion, evidencing even more the renal injury (once some authors consider Klotho is a renal injury biomarker). In heart tissue, klotho expression is reduced since the first 24h, but this is attenuated around the 4th week of reperfusion.ConclusionWe found that cardiac FGF23/Klotho axis dynamics are affected by renal I/R indicating a possible interaction between these two responses during cardiorenal syndrome.Support or Funding InformationFinancial Support: FAPESP 2015/19107‐5 and 2018/03089‐6.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.