Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

• Published in: Scientific reports 2019-04, Vol.9 (1), p.5848-5848, Article 5848
• Main Authors: Jeong, Geon, Kwon, Duk-Hwa, Shin, Sera, Choe, Nakwon, Ryu, Juhee, Lim, Yeong-Hwan, Kim, Jaetaek, Park, Woo Jin, Kook, Hyun, Kim, Young-Kook
• Format: Article
• Language: English
• Subjects: 13/89; 38/109; 38/90; 38/91; 631/208/200; 631/337/2019; 631/337/384/2568; Animals; Base Sequence; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Calcification; Calcification (ectopic); Calcium; Calcium - metabolism; Cells, Cultured; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Crystals; Gene Regulatory Networks; Humanities and Social Sciences; Humans; Hydroxyapatite; Localization; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Morbidity; multidisciplinary; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Rats; RNA Interference; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Sequence Alignment; Smooth muscle; Therapeutic applications; Transcription; Vascular Calcification - genetics; Vascular Calcification - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-42283-x

Vascular calcification is characterized by the accumulation of hydroxyapatite crystals, which is a result of aberrant mineral metabolism. Although many clinical studies have reported its adverse effects on cardiovascular morbidity, the molecular mechanism of vascular calcification, especially the involvement of long noncoding RNAs (lncRNAs), is not yet reported. From the transcriptomic analysis, we discovered hundreds of lncRNAs differentially expressed in rat vascular smooth muscle cells (VSMCs) treated with inorganic phosphate, which mimics vascular calcification. We focused on Lrrc75a-as1 and elucidated its transcript structure and confirmed its cytoplasmic localization. Our results showed that calcium deposition was elevated after knockdown of Lrrc75a-as1, while its overexpression inhibited calcium accumulation in A10 cells. In addition, Lrrc75a-as1 attenuated VSMCs calcification by decreasing the expression of osteoblast-related factors. These findings suggest that Lrrc75a-as1 acts as a negative regulator of vascular calcification, and may serve as a possible therapeutic target in vascular calcification.