A systematic review and meta-analysis of murine models of uremic cardiomyopathy

Soppert, Josefin; Frisch, Janina; Wirth, Julia; Hemmers, Christian; Boor, Peter; Kramann, Rafael; Vondenhoff, Sonja; Moellmann, Julia; Lehrke, Michael; Hohl, Mathias; Vorst, Emiel P. C. van der; Werner, Christian; Speer, Thimoteus; Maack, Christoph; Marx, Nikolaus; Jankowski, Joachim; Roma, Leticia Prates und Noels, Heidi (2022): A systematic review and meta-analysis of murine models of uremic cardiomyopathy. In: Kidney International, Bd. 101, Nr. 2: S. 256-273

Abstract

Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in single hit strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in multifactorial hit strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, multifactorial hit models more consistently induced cardiac hypertrophy and fibrosis compared to single hit kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can prime for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0085-2538
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 322900939