Abstract
MicroRNAs (miRs) are known to have an important role in modulating vascular biology. MiR21 was found to be involved in the pathogenesis of proliferative vascular disease. The role of miR21 in endothelial cells (ECs) has well studied in vitro, but the study in vivo remains to be elucidated. In this study, miR21 endothelial-specific knockout mice were generated by Cre/LoxP system. Compared with wild-type mice, the miR21 deletion in ECs resulted in structural and functional remodeling of aorta significantly, such as diastolic pressure dropping, maximal tension depression, endothelium-dependent relaxation impairment, an increase of opening angles and wall-thickness/inner diameter ratio, and compliance decrease, in the miR21 endothelial-specific knockout mice. Furthermore, the miR21 deletion in ECs induced down-regulation of collagen I, collagen III and elastin mRNA and proteins, as well as up-regulation of Smad7 and down-regulation of Smad2/5 in the aorta of miR21 endothelial-specific knockout mice. CTGF and downstream MMP/TIMP changes were also identified to mediate vascular remodeling. The results showed that miR21 is identified as a critical molecule to modulate vascular remodeling, which will help to understand the role of miR21 in vascular biology and the pathogenesis of vascular diseases.
Highlights
MircoRNAs are a class of,22 nucleotide non-coding RNAs that regulate gene expression of various kinds of cellular proteins by targeting their mRNA expression levels [1,2]
We found that miR21 specific deletion in endothelial cells (ECs) modulates vascular remodeling
The data showed that Smad7 as well as connective tissue growth factor (CTGF) and downstream matrix metalloproteinases (MMPs)/tissue inhibitors of matrix metalloproteinases (TIMPs) are involved in the effects of miR21 deletion in ECs
Summary
MircoRNAs (miRs) are a class of ,22 nucleotide non-coding RNAs that regulate gene expression of various kinds of cellular proteins by targeting their mRNA expression levels [1,2]. MiRs are being recognized to be expressed in the cardiovascular system, and evidence supports a role of miRs in vascular biology and the pathogenesis of artery disease [3] Among these miRs, MiR21 is found to participate in vascular remodeling by regulating proliferation, apoptosis and phenotype transformation of vascular smooth muscle cells (VSMCs) [4,5,6,7,8]. MiR21 expression was reduced in late-passage senescent human aorta ECs featuring reduced cell proliferation, enhanced apoptosis and inflammation and reduced eNOS [10]. These findings strongly suggest that miR21 have a crucial role in modulating EC biology
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