1. MiR-196a-5p hinders vascular smooth muscle cell proliferation and vascular remodeling via repressing BACH1 expression.
- Author
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Tong Y, Wang DD, Zhang YL, He S, Chen D, Wu YX, and Pang QF
- Subjects
- Animals, Humans, Male, Rats, Gene Expression Regulation, Hypertension metabolism, Hypertension genetics, Hypertension pathology, Rats, Inbred WKY, Basic-Leucine Zipper Transcription Factors metabolism, Basic-Leucine Zipper Transcription Factors genetics, Cell Proliferation genetics, MicroRNAs genetics, MicroRNAs metabolism, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology, Oxidative Stress, Rats, Inbred SHR, Vascular Remodeling genetics
- Abstract
Hyperproliferation of vascular smooth muscle cells (VSMCs) is a driver of hypertensive vascular remodeling. This study aimed to uncover the mechanism of BTB and CNC homology 1 (BACH1) and microRNAs (miRNAs) in VSMC growth and hypertensive vascular remodeling. With the help of TargetScan, miRWalk, miRDB, and miRTarBase online database, we identified that BACH1 might be targeted by miR-196a-5p, and overexpressed in VSMCs and aortic tissues from spontaneously hypertensive rats (SHRs). Gain- and loss-of-function experiments demonstrated that miR-196a-5p suppressed VSMC proliferation, oxidative stress and hypertensive vascular remodeling. Double luciferase reporter gene assay and functional verification showed that miR-196a-5p cracked down the transcription and translation of BACH1 in both Wistar Kyoto rats (WKYs) and SHRs. Silencing BACH1 mimicked the actions of miR-196a-5p overexpression on attenuating the proliferation and oxidative damage of VSMCs derived from SHRs. Importantly, miR-196a-5p overexpression and BACH1 knockdown cooperatively inhibited VSMC proliferation and oxidative stress in SHRs. Furthermore, miR-196a-5p, if knocked down in SHRs, aggravated hypertension, upregulated BACH1 and promoted VSMC proliferation, all contributing to vascular remodeling. Taken together, targeting miR-196a-5p to downregulate BACH1 may be a promising strategy for retarding VSMC proliferation and hypertensive vascular remodeling., (© 2024. The Author(s).)
- Published
- 2024
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