BACKGROUND: Uraemic cardiomyopathy, a process mainly associated with increased myocardial fibrosis, is the leading cause of death in chronic kidney disease patients and can be prevented by vitamin D receptor activators (VDRAs). Since some microRNAs (miRNAs) have emerged as regulators of the fibrotic process, we aimed to analyse the role of specific miRNAs in VDRA prevention of myocardial fibrosis as well as their potential use as biomarkers. METHODS: Wistar rats were nephrectomized and treated intraperitoneally with equivalent doses of two VDRAs: calcitriol and paricalcitol. Biochemical parameters, cardiac fibrosis, miRNA (miR-29b, miR-30c and miR-133b) levels in the heart and serum and expression of their target genes collagen I (COL1A1), matrix metalloproteinase 2 (MMP-2) and connective tissue growth factor (CTGF) in the heart were evaluated. RESULTS: Both VDRAs attenuated cardiac fibrosis, achieving a statistically significant difference in the paricalcitol-treated group. Increases in RNA and protein levels of COL1A1, MMP-2 and CTGF and reduced expression of miR-29b and miR-30c, known regulators of these pro-fibrotic genes, were observed in the heart of chronic renal failure (CRF) rats and were attenuated by both VDRAs. In serum, significant increases in miR-29b, miR-30c and miR-133b levels were observed in CRF rats, which were prevented by VDRA use. Moreover, vitamin D response elements were identified in the three miRNA promoters. CONCLUSIONS: VDRAs, particularly paricalcitol, attenuated cardiac fibrosis acting on COL1A1, MMP-2 and CTGF expression, partly through regulation of miR-29b and miR-30c. These miRNAs and miR-133b could be useful serum biomarkers for cardiac fibrosis and also potential new therapeutic targets.
BACKGROUND: Uraemic cardiomyopathy, a process mainly associated with increased myocardial fibrosis, is the leading cause of death in chronic kidney disease patients and can be prevented by vitamin D receptor activators (VDRAs). Since some microRNAs (miRNAs) have emerged as regulators of the fibrotic process, we aimed to analyse the role of specific miRNAs in VDRA prevention of myocardial fibrosis as well as their potential use as biomarkers. METHODS: Wistar rats were nephrectomized and treated intraperitoneally with equivalent doses of two VDRAs: calcitriol and paricalcitol. Biochemical parameters, cardiac fibrosis, miRNA (miR-29b, miR-30c and miR-133b) levels in the heart and serum and expression of their target genes collagen I (COL1A1), matrix metalloproteinase 2 (MMP-2) and connective tissue growth factor (CTGF) in the heart were evaluated. RESULTS: Both VDRAs attenuated cardiac fibrosis, achieving a statistically significant difference in the paricalcitol-treated group. Increases in RNA and protein levels of COL1A1, MMP-2 and CTGF and reduced expression of miR-29b and miR-30c, known regulators of these pro-fibrotic genes, were observed in the heart of chronic renal failure (CRF) rats and were attenuated by both VDRAs. In serum, significant increases in miR-29b, miR-30c and miR-133b levels were observed in CRF rats, which were prevented by VDRA use. Moreover, vitamin D response elements were identified in the three miRNA promoters. CONCLUSIONS: VDRAs, particularly paricalcitol, attenuated cardiac fibrosis acting on COL1A1, MMP-2 and CTGF expression, partly through regulation of miR-29b and miR-30c. These miRNAs and miR-133b could be useful serum biomarkers for cardiac fibrosis and also potential new therapeutic targets.
Authors: Márta Sárközy; Zsuzsanna Z A Kovács; Mónika G Kovács; Renáta Gáspár; Gergő Szűcs; László Dux Journal: Front Physiol Date: 2018-11-26 Impact factor: 4.566
Authors: Márta Sárközy; Renáta Gáspár; Ágnes Zvara; Andrea Siska; Bence Kővári; Gergő Szűcs; Fanni Márványkövi; Mónika G Kovács; Petra Diószegi; László Bodai; Nóra Zsindely; Márton Pipicz; Kamilla Gömöri; Krisztina Kiss; Péter Bencsik; Gábor Cserni; László G Puskás; Imre Földesi; Thomas Thum; Sándor Bátkai; Tamás Csont Journal: Sci Rep Date: 2019-02-04 Impact factor: 4.379
Authors: Bruna J Quintanilha; Bruna Z Reis; Graziela B Silva Duarte; Silvia M F Cozzolino; Marcelo M Rogero Journal: Nutrients Date: 2017-10-27 Impact factor: 5.717
Authors: Laura Gisbert-Ferrándiz; Jesús Cosín-Roger; Carlos Hernández; Dulce C Macias-Ceja; Dolores Ortiz-Masiá; Pedro Salvador; Juan V Esplugues; Joaquín Hinojosa; Francisco Navarro; Sara Calatayud; María D Barrachina Journal: Nutrients Date: 2020-04-01 Impact factor: 5.717