ArticleCirculation2016
Inhibition of Aberrant MicroRNA-133a Expression in Endothelial Cells by Statin Prevents Endothelial Dysfunction by Targeting GTP Cyclohydrolase 1 in Vivo.
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Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed, 127 citations in OpenAlex.
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- MicroRNA-Mediated Regulation of Vascular Endothelium: From Pro-Inflammation to Atherosclerosis.International journal of molecular sciences · 2025Review
- Treatment of endothelial cell dysfunction in atherosclerosis: a new perspective integrating traditional and modern approaches.Frontiers in physiology · 2025Review
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- The Role of Antioxidants in the Therapy of Cardiovascular Diseases-A Literature Review.Nutrients · 2024Review
- Citronellal improves endothelial dysfunction by affecting the stability of the GCH1 protein.Acta biochimica et biophysica Sinica · 2024Article
- Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.Nature communications · 2024Article
- Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling.Current vascular pharmacology · 2024Article
- S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming.EMBO reports · 2024Article
- miRNAs Epigenetic Tuning of Wall Remodeling in the Early Phase after Myocardial Infarction: A Novel Epidrug Approach.International journal of molecular sciences · 2023Review
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- State-of-the-art polyetheretherketone three-dimensional printing and multifunctional modification for dental implants.Frontiers in bioengineering and biotechnology · 2023Review
- Citronellal Attenuates Oxidative Stress-Induced Mitochondrial Damage through TRPM2/NHE1 Pathway and Effectively Inhibits Endothelial Dysfunction in Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2022Article
- Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression.Scientific reports · 2022Article
- miR-548j-5p regulates angiogenesis in peripheral artery disease.Scientific reports · 2022Article
- Research progress in endothelial cell injury and repair.Frontiers in pharmacology · 2022Review
- Cardiac Remodeling After Myocardial Infarction: Functional Contribution of microRNAs to Inflammation and Fibrosis.Frontiers in cardiovascular medicine · 2022Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Peng LiFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Ya-Ling YinFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Tao GuoFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Xue-Ying SunFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Hui MaFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Mo-Li ZhuFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Fan-Rong ZhaoFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Ping XuFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Yuan ChenFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Guang-Rui WanFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Fan JiangFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Qi-Sheng PengFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Chao LiuFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Li-Ying LiuFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.).
Shuang-Xi WangFrom School of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, China (P.L., Y.-L.Y., M.-L.Z., F.-R.Z., P.X., G.-R.W., S.-X.W.); The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China (T.G., H.M., Y.C., F.J., S.-X.W.); Department of Pharmacology, School of Pharmacy, Central South University, Changsha, China (X.-Y.S., L.-Y.L.); The Key Laboratory for Zoonosis Research, Institute of Zoonosis, Jilin University, Changchun, China (Q.-S.P.); and Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China (C.L.). shuangxiwang@sdu.edu.cn.
Central South University · CNJilin University · CNXinxiang Medical University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase uncoupling in endothelial dysfunction. MicroRNAs (miRs) are a class of regulatory RNAs that negatively regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation.
methodsEndothelial function was assessed by measuring acetylcholine-induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization.
resultsWe first demonstrated that GCH1 mRNA is a target of miR-133a. In endothelial cells, miR-133a was robustly induced by cytokines/oxidants and inhibited by lovastatin. Furthermore, lovastatin upregulated GCH1 and tetrahydrobiopterin, and recoupled endothelial nitric oxide synthase in stressed endothelial cells. These actions of lovastatin were abolished by enforced miR-133a expression and were mirrored by a miR-133a antagomir. In mice, hyperlipidemia- or hyperglycemia-induced ectopic miR-133a expression in the vascular endothelium, reduced GCH1 protein and tetrahydrobiopterin levels, and impaired endothelial function, which were reversed by lovastatin or miR-133a antagomir. These beneficial effects of lovastatin in mice were abrogated by in vivo miR-133a overexpression or GCH1 knockdown. In rats, multiple cardiovascular risk factors including hyperglycemia, dyslipidemia, and hyperhomocysteinemia resulted in increased miR-133a vascular expression, reduced GCH1 expression, uncoupled endothelial nitric oxide synthase function, and induced endothelial dysfunction, which were prevented by lovastatin.
conclusionsStatin inhibits aberrant miR-133a expression in the vascular endothelium to prevent endothelial dysfunction by targeting GCH1. Therefore, miR-133a represents an important therapeutic target for preventing cardiovascular diseases.
Indexed as
AnimalsDisease Models, AnimalEndothelial CellsGTP CyclohydrolaseHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatinMiceMicroRNAsNitric OxideNitric Oxide Synthase Type IIIRatsRisk FactorsRNA, MessengerGch1 protein, mouseGTP CyclohydrolaseHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatinMicroRNAsMIRN133 microRNA, ratNitric OxideNitric Oxide Synthase Type IIIRNA, Messengerendothelial cellsGTP cyclohydrolasehydroxymethylglutaryl-CoA reductase inhibitorsmicMIRN133nitric oxide synthaseroRNA, rattype III
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