Mechanical stretch aggravates vascular smooth muscle cell apoptosis and vascular remodeling by downregulating EZH2. 2022

Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.

Enhancer of zeste homolog 2 (EZH2) was recently found to play an important role in cardiovascular disease. However, the role of EZH2 in vascular remodeling induced by mechanical stretch is poorly understood. The aim of the present work was to investigate the role of EZH2 in regulating smooth muscle cell function through mechanical stretch assays and to explore the underlying mechanisms. WT C57BL/6 J mice underwent sham surgery or abdominal aortic constriction. The level of EZH2 expression was determined by Western blotting and immunohistochemical staining. We demonstrated the thickness of vascular remodeling by HE staining. JASPAR was used to predict transcription factors that could affect EZH2. Chromatin immunoprecipitation was used to substantiate the DNAprotein interactions. Promoter luciferase assays were performed to demonstrate the activity of the transcription factors. We found that in vivo, AAC significantly reduced EZH2 protein levels in the thoracic aorta. Smooth muscle-specific overexpression of EZH2 was sufficient to attenuate the AAC-induced reduction in trimethylation of Lys-27 in histone 3 and thickening of the arterial media. Administration of GSK-J4 (an inhibitor of H3K27me3 demethylase) induced the same effects. In addition, we found that mechanical stretch regulated the expression of EZH2 through the Yes-associated protein (YAP)- transcriptional factor TEA domain 1 (TEAD) pathway. TEAD1 bound directly to the promoter of EZH2, and blocking the YAP-TEAD1 interaction inhibited EZH2 downregulation due to mechanical stretch. This study reveals that mechanical stretch downregulates EZH2 through the YAP-TEAD1 pathway, thereby aggravating smooth muscle cell apoptosis and vascular remodeling.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D006657 Histones Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D000071221 Enhancer of Zeste Homolog 2 Protein A histone-lysine N-methyltransferase and catalytic subunit of Polycomb Repressive Complex 2. It methylates LYSINE 9 (H3K9me) and LYSINE 27 (H3K27me) of HISTONE H3, leading to transcriptional repression of the affected target gene. EZH2 also methylates non-histone proteins such as GATA4 TRANSCRIPTION FACTOR and the nuclear receptor RORA. It regulates CIRCADIAN CLOCKS via histone methylation of circadian protein gene PROMOTER REGIONS, and its repressive activity is also important for the identity and differentiation of EMBRYONIC STEM CELLS. Enhancer of Zeste Homolog 2,Histone-Lysine N-Methyltransferase EZH2,Lysine N-Methyltransferase-6,EZH2, Histone-Lysine N-Methyltransferase,Histone Lysine N Methyltransferase EZH2,Lysine N Methyltransferase 6
D000091102 YAP-Signaling Proteins Signal transducing adaptor proteins that were initially identified by their association with YES PROTO-ONCOGENE PROTEIN. They are downstream components of the HIPPO-SIGNALING PATHWAY, and act as transcriptional co-activators for TEAD TRANSCRIPTION FACTORS. YAP Intracellular Signaling Proteins,Yes-Associated Proteins,YAP Signaling Proteins,Yes Associated Proteins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
May 2002, American journal of physiology. Heart and circulatory physiology,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
January 2006, Journal of vascular research,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
May 2008, Current opinion in hematology,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
January 2012, Cardiovascular research,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
January 2018, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
December 2018, Circulation research,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
November 2017, Scientific reports,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
June 2003, Endocrinology,
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
February 2018, Clinical science (London, England : 1979),
Hong-Yu Zhong, and Chong Yuan, and Xiao-Lin Liu, and Qian-Qian Wang, and Xiao Li, and Ya-Chao Zhao, and Xuan Li, and Dong-Dong Liu, and Teng-Fei Zheng, and Mei Zhang
May 2010, Journal of the American College of Cardiology,
Copied contents to your clipboard!