Author + information
- Chen Chen,
- Hengzhi Du,
- Zhongwei Yin and
- Dao Wen Wang
It has been unclear whether the elevated levels of the circulating miR-320a in coronary artery disease patients is due to environmental influence or genetic basis.
The expression of miR-320a was manipulated by rAAV system in vivo. Bioinformatic analysis, Luciferase reporter assay and Chromatin Conformation Capture assay were perfomed to identify the association of rs13282783 with hyperlipidemia. Finally, genome editing of rs13282783 in L02 cells revealed its function.
By rAAV-mediated loss- and gain-of-function studies in mouse liver, we revealed that elevated miR-320a is sufficient to aggravate diet-induced hyperlipidemia and hepatic steatosis. Then, we analyzed the data from published GWAS and identified the rs12541335 associated with hyperlipidemia. We demonstrated that the rs13282783 T allele indeed obligated the silencer activity by preventing the repressor ZFP161 and co-repressor HDAC2 from binding to DNA that led to miR-320a up-regulation. We further confirmed this genetic connection on an independent population and through direct genome editing in liver cells.
Besides environmental (diet) influence, we established a genetic component in the regulation of miR-320a expression, which suggest a potential therapeutic avenue to treat coronary artery disease by blocking miR-320a in patient liver.
Sunday, March 29, 2020, 8:51 a.m.-9:01 a.m.
Session Title: Highlighted Original Research: Vascular Medicine and the Year in Review
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 906-10
- 2020 American College of Cardiology Foundation