Abstract
Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5/6 nephrectomy group (5/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.
Highlights
Cardiovascular disease is the most common complication of chronic kidney disease (CKD) and the main cause of death among dialysis patients [1,2,3]
Eight-week-old mice were randomly assigned to the following experimental groups: sham group, 5/6 nephrectomy group (5/6Nx) (Figure 1A,a), pole ligation group (Figure 1A,b), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR) (Figure 1A,c), and adenine group
Eight-week-old mice were randomly assigned to the following experimental groups: sham groups (n = 14), 5/6 nephrectomy group (5/6Nx) (n = 45) (Figure 1A,a), pole ligation group (n = 34) (Figure 1A,b), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR) (n = 20) (Figure 1A,c), and adenine group (n = 15)
Summary
Cardiovascular disease is the most common complication of chronic kidney disease (CKD) and the main cause of death among dialysis patients [1,2,3]. A large number of patients with kidney disease die within 3 years after the diagnosis of uraemic cardiomyopathy (UCM) [4]. The rat is an extremely useful model for studying cardiomyopathy of renal failure [6, 7], there are currently many genetic manipulations in mice, and it is easier to perform additional genetic manipulations in the mouse system. The 5/6 nephrectomy (5/6Nx) [8,9,10], uninephrectomy plus contralateral ischemia followed by reperfusion (IR) [11], pole ligation [12] and adenine diet models [13] of uraemic cardiomyopathy in mice have been reported in recent years. There is no research comparing the advantages and disadvantages of various mouse UCM models
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