Aberration methylation of miR-34b was involved in regulating vascular calcification by targeting Notch1.

Aberration methylation of miR-34b was involved in regulating vascular calcification by targeting Notch1. Aging (Albany NY). 2019 May 25;: Authors: Lin X, Li F, Xu F, Cui RR, Xiong D, Zhong JY, Zhu T, Shan SK, Wu F, Xie XB, Liao XB, Yuan LQ Abstract Vascular calcification is one of the most important factors for cardiovascular and all-cause mortality in patients with end-stage renal diseases (ESRD). The current study was aimed to investigate the function and mechanisms of miR-34b on the calcification of vascular smooth muscle cells (VSMCs) both in vitro and in vivo. We found that the expression of miR-34b was significantly suppressed in VSMCs with high inorganic phosphate (Pi) treatment, as well as mouse arteries derived from 5/6 nephrectomy with a high-phosphate diet (0.9% Pi, 5/6 NTP) and human renal arteries from uraemia patients. Overexpression of miR-34b alleviated calcification of VSMCs, while VSMCs calcification was enhanced by inhibiting the expression of miR-34b. Bisulphite sequencing PCR (BSP) uncovered that CpG sites upstream of miR-34b DNA were hypermethylated in calcified VSMCs and calcified arteries due to 5/6 NTP, as well as calcified renal arterial tissues from uraemia patients. Meantime, increased DNA methyltransferase 3a (DNMT3a) resulted in the hypermethylation of miR-34b in VSMCs, while 5-aza-2'-deoxycytidine (5-aza) reduced the methylation rate of miR-34b and restored the expression of miR-34b in VSMCs. When DNMT3...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research