MiR-191 inhibit angiogenesis after acute ischemic stroke targeting VEZF1.

Abstract

Acute ischemic stroke (AIS) is a major public health problem in China. Impaired angiogenesis plays crucial roles in the development of ischemic cerebral injury. Recent studies have identified that microRNAs (miRNAs) are important regulators of angiogenesis, but little is known the exact effects of angiogenesis-associated miRNAs in AIS. In the present study, we detected the expression levels of angiogenesis-associated miRNAs in AIS patients, middle cerebral artery occlusion (MCAO) rats, and oxygen-glucose deprivation/reoxygenation (OGD/R) human umbilical vein endothelial cells (HUVECs). MiR-191 was increased in the plasma of AIS patients, OGD/R HUVECs, and the plasma and brain of MCAO rats. Over-expression of miR-191 promoted apoptosis, but reduced the proliferation, migration, tube-forming and spheroid sprouting activity in HUVECs OGD/R model. Mechanically, vascular endothelial zinc finger 1 (VEZF1) was identified as the direct target of miR-191, and could be regulated by miR-191 at post-translational level. In vivo studies applying miR-191 antagomir demonstrated that inhibition of miR-191 reduced infarction volume in MCAO rats. In conclusion, our data reveal a novel role of miR-191 in promoting ischemic brain injury through inhibiting angiogenesis via targeting VEZF1. Therefore, miR-191 may serve as a biomarker or a therapeutic target for AIS.

• Authors: Kang Du, Can Zhao, Li Wang, Yue Wang, Kang-Zhen Zhang, Xi-Yu Shen, Hui-Xian Sun, Wei Gao, Xiang Lu
• Journal: Aging (Aging (Albany NY)) Vol. 11 Issue 9 Pg. 2762-2786 (05 07 2019) ISSN: 1945-4589 [Electronic] United States
• PMID: 31064890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• DNA-Binding Proteins
• MIRN191 microRNA, human
• MicroRNAs
• Transcription Factors
• VEZF1 protein, human

Topics

• Aged
• Animals
• Biomarkers
• Brain Ischemia (metabolism, pathology)
• DNA-Binding Proteins (metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells
• Humans
• Infarction, Middle Cerebral Artery
• Male
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neovascularization, Physiologic (physiology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Spheroids, Cellular
• Stroke (metabolism, pathology)
• Transcription Factors (metabolism)