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MALAT1 affects hypoxia-induced vascular endothelial cell injury and autophagy by regulating miR-19b-3p/HIF-1α axis

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Abstract

Cardiovascular disease has become the leading cause of death in the world. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in cardiovascular disease, such as stroke. However, the role of MALAT1 in hypoxia (HYP)-induced vascular endothelial cells (VECs) remains unclear. In the present study, HYP-treated human umbilical vein endothelial cells (HUVECs) were utilized to simulate HYP-induced VEC injury. It was found that after HYP treatment, the levels of MALAT1 and hypoxia-induced factor-1 (HIF-1α) in HUVECs were upregulated, while the level of miR-19b-3p was downregulated. Knockdown of MALAT1 with siRNA significantly reduced the HIF-1α level induced by HYP. In addition, MALAT1 knockdown inhibited HYP-induced HUVECs apoptosis, autophagy and inflammation. The overexpression of HIF-1α overcame the effect of MALAT1 knockdown. Mechanism analysis showed that MALAT1-targeted miR-19b-3p and then regulated downstream HIF-1α. MALAT1 knockdown increased the level of miR-19b-3p in cells, and increased miR-19b-3p further inhibited the expression of HIF-1α, thereby reducing the HYP-induced HUVECs apoptosis, autophagy and inflammation. Taken together, these results suggest that MALAT1 may be a potential target for mitigating HYP-induced endothelial cell injury.

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  1. Department of Cardiothoracic Surgery, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, China

    Huzi Liu

  2. Department of Outpatient, Shanxi Cardiovascular Hospital (Institute), The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030024, China

    Chunli Shi

  3. Department of Cardiovascular Surgery, Shanxi Cardiovascular Hospital (Institute), The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Medical University, No. 18, Yifen Street, Wanbailin District, Taiyuan, 030024, Shanxi, China

    Yongzhi Deng

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Liu, H., Shi, C. & Deng, Y. MALAT1 affects hypoxia-induced vascular endothelial cell injury and autophagy by regulating miR-19b-3p/HIF-1α axis. Mol Cell Biochem 466, 25–34 (2020). https://doi.org/10.1007/s11010-020-03684-z

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