Abstract
Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of microRNA-27a-3p (miR-27a-3p) causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of miR-27a-3p in A10 cells. The transcript level was also reduced in vitamin D3-administered mouse aortas. miR-27a-3p mimic reduced calcium deposition, whereas miR-27a-3p inhibitor increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and miR-27a-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-27a-3p-induced reduction of calcium deposition. Our results suggest that reduction of miR-27a-3p may contribute to the development of vascular calcification by de-repression of ATF3.
Highlights
In abnormal circumstances, hydroxyapatite, a calcium phosphate mineral, can be deposited in blood vessels, which is linked to aging and cardiovascular or metabolic diseases such as atherosclerosis, chronic kidney disease, and diabetes.[1]
Screening of Vascular Calcification-Associated miRNAs and. Their Possible Targets To search for pairs of miRNAs and their targets, we performed miRNA and mRNA microarrays in Pi-treated rat VSMCs (rVSMCs)
The present study suggests a novel mechanism for miR-27a-3p and its target Atf[3] in the regulation of vascular calcification
Summary
Hydroxyapatite, a calcium phosphate mineral, can be deposited in blood vessels, which is linked to aging and cardiovascular or metabolic diseases such as atherosclerosis, chronic kidney disease, and diabetes.[1] This phenomenon, called vascular calcification, causes remodeling of the blood vessels, resulting in an increase in stiffness. Because this abnormal rigidity itself can cause secondary fatal diseases such as ischemia of distal tissue or rupture, vascular calcification is often considered an independent risk factor for cardiovascular events.[2]. Induces vascular stiffness, hypertension, and an increase in pulse pressure, which can cause diastolic dysfunction of the heart.[3,4,5] While atherosclerosis is highly linked with intimal calcification, diabetes (types 1 and 2) and its associated metabolic syndrome as well as chronic renal failure are associated with both types of calcification (intimal and medial).[2]
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