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ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation.
iScience 2019; 19:872-882I

Abstract

Vascular smooth muscle cell (VSMC) proliferation promotes intimal hyperplasia (IH) in occluding vascular diseases. Here we identified a positive role of ALDH1A3 (an aldehyde dehydrogenase) in this pro-IH process. The expression of ALDH1A3, but not that of 18 other isoforms of the ALDH family, was substantially increased in cytokine-stimulated VSMCs. PDGF(BB) stimulated VSMC total ALDH activity and proliferation, whereas ALDH1A3 silencing abolished this effect. ALDH1A3 silencing also diminished the expression of two matricellular proteins (TNC1 and ESM1), revealing a previously unrecognized ALDH1A3 function. Loss-of-function experiments demonstrated that TNC1 and ESM1 mediated ALDH1A3's pro-proliferative function via activation of AKT/mTOR and/or MEK/ERK pathways. Furthermore, ALDH inhibition with disulfiram blocked VSMC proliferation/migration in vitro and decreased TNC1 and ESM1 and IH in angioplasty-injured rat carotid arteries. Thus, ALDH1A3 promotes VSMC proliferation at least partially through TNC1/ESM1 upregulation; dampening excessive ALDH1A3 activity represents a potential approach to IH mitigation.

Authors+Show Affiliations

Department of Surgery, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.Department of Surgery, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology & Cell Biology, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.Department of Surgery, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology & Cell Biology, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.Department of Physiology & Cell Biology, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.Department of Surgery, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology & Cell Biology, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: lianwang.guo@osumc.edu.Department of Surgery, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: kc.kent@osumc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31513972

Citation

Xie, Xiujie, et al. "ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation." IScience, vol. 19, 2019, pp. 872-882.
Xie X, Urabe G, Marcho L, et al. ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation. iScience. 2019;19:872-882.
Xie, X., Urabe, G., Marcho, L., Stratton, M., Guo, L. W., & Kent, C. K. (2019). ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation. IScience, 19, pp. 872-882. doi:10.1016/j.isci.2019.08.044.
Xie X, et al. ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation. iScience. 2019 Sep 27;19:872-882. PubMed PMID: 31513972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation. AU - Xie,Xiujie, AU - Urabe,Go, AU - Marcho,Lynn, AU - Stratton,Matthew, AU - Guo,Lian-Wang, AU - Kent,Craig K, Y1 - 2019/08/27/ PY - 2019/04/11/received PY - 2019/06/09/revised PY - 2019/08/21/accepted PY - 2019/9/13/pubmed PY - 2019/9/13/medline PY - 2019/9/13/entrez KW - Molecular Biology KW - Molecular Mechanism of Behavior KW - Pathophysiology KW - Vascular Remodeling SP - 872 EP - 882 JF - iScience JO - iScience VL - 19 N2 - Vascular smooth muscle cell (VSMC) proliferation promotes intimal hyperplasia (IH) in occluding vascular diseases. Here we identified a positive role of ALDH1A3 (an aldehyde dehydrogenase) in this pro-IH process. The expression of ALDH1A3, but not that of 18 other isoforms of the ALDH family, was substantially increased in cytokine-stimulated VSMCs. PDGF(BB) stimulated VSMC total ALDH activity and proliferation, whereas ALDH1A3 silencing abolished this effect. ALDH1A3 silencing also diminished the expression of two matricellular proteins (TNC1 and ESM1), revealing a previously unrecognized ALDH1A3 function. Loss-of-function experiments demonstrated that TNC1 and ESM1 mediated ALDH1A3's pro-proliferative function via activation of AKT/mTOR and/or MEK/ERK pathways. Furthermore, ALDH inhibition with disulfiram blocked VSMC proliferation/migration in vitro and decreased TNC1 and ESM1 and IH in angioplasty-injured rat carotid arteries. Thus, ALDH1A3 promotes VSMC proliferation at least partially through TNC1/ESM1 upregulation; dampening excessive ALDH1A3 activity represents a potential approach to IH mitigation. SN - 2589-0042 UR - https://www.unboundmedicine.com/medline/citation/31513972/ALDH1A3_Regulations_of_Matricellular_Proteins_Promote_Vascular_Smooth_Muscle_Cell_Proliferation L2 - https://linkinghub.elsevier.com/retrieve/pii/S2589-0042(19)30322-0 DB - PRIME DP - Unbound Medicine ER -