title: Long Noncoding RNA-GAS5: A Novel Regulator of Hypertension-Induced Vascular Remodeling.
abstract: 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.
authors.affiliation: 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.).
authors.forename: Yang-Ning-Zhi
authors.initials: YN
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Kun
authors.initials: K
authors.lastname: Shan
authors.affiliation: 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.).
authors.forename: Mu-Di
authors.initials: MD
authors.lastname: Yao
authors.affiliation: 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.).
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.affiliation: 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.).
authors.forename: Jia-Jian
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.).
authors.forename: Ban
authors.initials: B
authors.lastname: Liu
authors.affiliation: 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.).
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: 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.).
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 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.). yanbiao1982@hotmail.com jqin710@vip.sina.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: 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.). yanbiao1982@hotmail.com jqin710@vip.sina.com.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D014162:Transfection; D066253:Vascular Remodeling / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D020537:RNA, Small Nucleolar; D051176:beta Catenin; C109857:growth arrest specific transcript 5
keywords: GAS5; long noncoding RNA; spontaneous hypertension; vascular remodeling; β-catenin signaling