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Published on: September 28, 2015
Endothelial MicroRNA-214 Confers Angiotensin II Hypertension by Targeting eNOS in Mice
Shuzhen Li1,2,3, Bing Liu1,2,3, Shuang Kang1,2,3
1Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Introduction:
MicroRNAs have been increasingly recognized for their roles in cardiovascular diseases. Among these microRNAs, miR-214 was reported to be involved in hypertension. However, the role of endothelial miR-214 in hypertension is still unknown. The aim of this study was to determine the role of cell-specific miR-214 on regulating blood pressure, as well as the potential mechanisms.
Methods:
We detected the levels of miR-214 in hypertensive mice and cultured mouse aortic endothelial cells (MAECs). In addition, mouse miR-214 inhibitor, miR-214 mimics, vascular endothelial cell-specific miR-214-deficient mice, smooth muscle cell-specific miR-214-deficient mice, renal proximal tubule cell-deficient mice, and various cellular and molecular techniques were employed to define the role of miR-214 in Ang II-induced hypertension.
Results:
In mice and MAECs, Ang II significantly enhanced miR-214 levels, and anti-miR-214 markedly attenuated Ang II hypertension in line with enhanced eNOS/p-eNOS in aorta. Then, we generated vascular endothelial cell-specific miR-214 knockout mice and found an antihypertensive phenotype in endothelial miR-214 conditional knockout mice after Ang II treatment. In normotensive animals and MAECs, exogenous miR-214 administration reduced eNOS expression at protein and mRNA levels; in contrast, anti-miR-214 played an opposite role in regulating eNOS. By luciferase assay, our results confirmed that eNOS was a direct target gene for miR-214 in endothelial cells. However, smooth muscle cell-specific or renal tubular cell-specific deletion of miR-214 did not alter Ang II-induced hypertension.
Conclusion:
Our findings suggested that endothelial miR-214 promoted Ang II hypertension by targeting eNOS in mice, which increased the understanding on the pathogenic mechanism of hypertension.
Insights
Endothelial miR-214 promotes hypertension by targeting eNOS. This study clarifies the role of microRNAs in cardiovascular disease, specifically in the context of high blood pressure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hypertension Research
Background:
- MicroRNAs are increasingly recognized for their roles in cardiovascular diseases.
- miR-214 has been implicated in hypertension, but its specific role in endothelial cells remains unclear.
- Understanding cell-specific microRNA functions is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To determine the role of endothelial cell-specific miR-214 in regulating blood pressure.
- To investigate the underlying molecular mechanisms by which miR-214 influences hypertension.
- To identify potential therapeutic targets for hypertension based on miR-214 function.
Main Methods:
- Detection of miR-214 levels in hypertensive mouse models and cultured mouse aortic endothelial cells (MAECs).
- Utilized miR-214 inhibitors, mimics, and cell-specific knockout mice (endothelial, smooth muscle, renal tubular).
- Employed various cellular and molecular techniques, including luciferase assays, to define miR-214's role in Ang II-induced hypertension.
Main Results:
- Angiotensin II (Ang II) significantly increased miR-214 levels in mice and MAECs.
- Inhibition of miR-214 attenuated Ang II-induced hypertension and enhanced eNOS/p-eNOS expression.
- Endothelial cell-specific miR-214 knockout mice exhibited an antihypertensive phenotype; smooth muscle or renal cell-specific deletion had no effect.
- eNOS was confirmed as a direct target gene of miR-214 in endothelial cells.
Conclusions:
- Endothelial miR-214 promotes Ang II-induced hypertension by targeting and downregulating eNOS.
- This study elucidates a key pathogenic mechanism in hypertension involving endothelial miR-214.
- Findings contribute to a deeper understanding of microRNA involvement in cardiovascular disease progression.
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