Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

Geon Jeong; Duk Hwa Kwon; Sera Shin; Nakwon Choe; Juhee Ryu; Yeong Hwan Lim; Jaetaek Kim; Woo Jin Park; Hyun Kook; Young Kook Kim

doi:10.1038/s41598-019-42283-x

Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

Geon Jeong, Duk Hwa Kwon, Sera Shin, Nakwon Choe, Juhee Ryu, Yeong Hwan Lim, Jaetaek Kim, Woo Jin Park, Hyun Kook, Young Kook Kim

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

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.

Original language	English
Article number	5848
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-42283-x
State	Published - 1 Dec 2019

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title = "Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification",

abstract = "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.",

author = "Geon Jeong and Kwon, {Duk Hwa} and Sera Shin and Nakwon Choe and Juhee Ryu and Lim, {Yeong Hwan} and Jaetaek Kim and Park, {Woo Jin} and Hyun Kook and Kim, {Young Kook}",

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doi = "10.1038/s41598-019-42283-x",

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T1 - Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

AU - Jeong, Geon

AU - Kwon, Duk Hwa

AU - Shin, Sera

AU - Choe, Nakwon

AU - Ryu, Juhee

AU - Lim, Yeong Hwan

AU - Kim, Jaetaek

AU - Park, Woo Jin

AU - Kook, Hyun

AU - Kim, Young Kook

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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SN - 2045-2322

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JO - Scientific Reports

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Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

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