长链非编码RNA-GAS5：高血压诱导血管重塑的新型调节因子
Long Noncoding RNA-GAS5: A Novel Regulator of Hypertension-Induced Vascular Remodeling.
作者信息
Wang Yang-Ning-Zhi, Shan Kun, Yao Mu-Di, Yao Jin, Wang Jia-Jian, Li Xiang, Liu Ban, Zhang Yang-Yang, Ji Yong, Jiang Qin, Yan Biao
机构信息
From the Eye Hospital, Nanjing Medical University, China (Y.-N.-Z.W., K.S., M.-D.Y., J.Y., Q.J.); Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University, China (J.-J.W.); Department of Cardiology, the first Affiliated Hospital, Chongqin Medical University, China (X.L.); Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (B.L.); Department of Cardiac Surgery, the first School of Clinical Medicine, Nanjing Medical University, China (Y.-Y.Z.); Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, China (Y.J.); and Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University, China (B.Y.).
出版信息
Hypertension. 2016 Sep;68(3):736-48. doi: 10.1161/HYPERTENSIONAHA.116.07259. Epub 2016 Jul 18.
Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension.
血管重塑是高血压的一个重要病理特征，会导致血管阻力增加和顺应性降低。内皮细胞（EC）和血管平滑肌细胞（VSMC）功能障碍参与了血管重塑过程。长链非编码RNA是EC和VSMC功能的潜在调节因子。在此，我们确定长链非编码RNA生长停滞特异性5（GAS5）是否参与高血压相关的血管重塑。我们发现，如视网膜新生血管形成增加和毛细血管渗漏所示，GAS5敲低加剧了高血压诱导的微血管功能障碍。GAS5调节包括尾动脉、颈动脉、肾动脉和胸主动脉在内的动脉重塑。GAS5主要在内皮细胞和平滑肌细胞中表达，其表达在高血压中显著下调。GAS5敲低在体内和体外均影响内皮细胞活化、内皮细胞增殖、VSMC表型转化以及EC-VSMC通讯。从机制上讲，GAS5通过β-连环蛋白信号传导调节EC和VSMC功能。本研究确定GAS5是高血压中的关键调节因子，并证明了基因治疗和药物开发在治疗高血压方面的潜力。
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