ABSTRACT
Background
Inflammatory response of human vascular smooth muscle cells (hVSMCs) is a driving factor in hypertension progression. It has been reported that miR-3646 was significantly up-regulated in serum samples from patients with coronary artery disease and acute myocardial infarction mice. However, its role and underlying molecular mechanism related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs remain unclear.
Objective
We aimed to explore the potential molecular mechanisms related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs.
Methods
Ang II–induced hypertension model was established after hVSMCs treated with 1 μM Ang II at 24 h. The interaction between microRNA 3646 (miR-3646) and cytochrome P450 2J2 (CYP2J2) was assessed by dual-luciferase reporter gene assay. MTS assay, Lipid Peroxidation MDA Assay Kit, ELISA, Western blot, and qRT-PCR were performed to examine viability, malondialdehyde (MDA) level, inflammatory cytokine levels, and the level of genes and proteins.
Results
Our findings illustrated that miR-3646 was up-regulated but CYP2J2 was down-regulated in Ang II–induced hVSMCs. Mechanically, miR-3646 negatively targeted to CYP2J2 in Ang II–induced hVSMCs. These findings indicated that miR-3646 regulated inflammatory response of Ang II–induced hVSMCs via targeting CYP2J2. Moreover, functional researches showed that CYP2J2 overexpression alleviated inflammatory response of Ang II–induced hVSMCs via epoxyeicosatrienoic acids/peroxisome proliferator-activated receptor-γ (EETs/PPARγ) axis, and miR-3646 aggravated inflammatory response of Ang II–induced hVSMCs via mediating CYP2J2/EETs axis.
Conclusion
MiR-3646 accelerated inflammatory response of Ang II–induced hVSMCs via CYP2J2/EETs axis. Our findings illustrated the specific molecular mechanism of miR-3646 regulating hypertension.
Acknowledgments
We would like to give our sincere gratitude to the reviewers for their constructive comments.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Ethics approval and consent to participate
The ethics committee of Xiangya Hospital, Central South University approved our study.
Data availability statement
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.