View : 472 Download: 123
2 '-5 ' oligoadenylate synthetase-like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability
- Title
- 2 '-5 ' oligoadenylate synthetase-like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability
- Authors
- Kim, Tae Kyeong; Jeon, Sejin; Park, Seonjun; Sonn, Seong-Keun; Seo, Seungwoon; Suh, Joowon; Jin, Jing; Kweon, Hyae Yon; Kim, Sinai; Moon, Shin Hye; Kweon, Okhee; Koo, Bon-Hyeock; Kim, Nayoung; Lee, Hae-Ock; Kim, Young-Myeong; Kim, Young-Joon; Park, Sung Ho; Oh, Goo Taeg
- Ewha Authors
- 오구택; 전세진; 서주원
- SCOPUS Author ID
- 오구택; 전세진; 서주원
- Issue Date
- 2022
- Journal Title
- NATURE COMMUNICATIONS
- ISSN
- 2041-1723
- Citation
- NATURE COMMUNICATIONS vol. 13, no. 1
- Publisher
- NATURE PORTFOLIO
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Maintaining optimal eNOS levels is important during cardiovascular events, although little is known regarding the mechanism of eNOS protection. Here, the authors show a regulatory role of endothelial OASL1 in maintaining eNOS mRNA stability and vascular biology under atheroprone conditions. Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2 '-5 ' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-kappa B activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease.
- DOI
- 10.1038/s41467-022-34433-z
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
-
s41467-022-34433-z.pdf(4.33 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML