Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype DOI Creative Commons

Laura Lecce,

Yang Xu,

Bhargavi V’Gangula

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(15)

Published: Aug. 1, 2021

Endothelial-mesenchymal transition (EndMT) is associated with various cardiovascular diseases and in particular atherosclerosis plaque instability. However, the molecular pathways that govern EndMT are poorly defined. Specifically, role of epigenetic factors histone deacetylases (HDACs) controlling atherosclerotic phenotype remains unclear. Here, we identified deacetylation, specifically mediated by HDAC9 (a class IIa HDAC), as playing an important both atherosclerosis. Using vitro models, found HDAC inhibition sustained expression endothelial proteins mitigated increase mesenchymal proteins, effectively blocking EndMT. Similarly, ex vivo genetic knockout Hdac9 cells prevented preserved a more endothelial-like phenotype. In vivo, atherosclerosis-prone mice endothelial-specific showed reduced significantly area. Furthermore, these displayed favorable phenotype, lipid content increased fibrous cap thickness. Together, findings indicate contributes to vascular pathology promoting Our study provides evidence for pathological link among EndMT, HDAC9, suggests targeting may be beneficial stabilization or slowing progression disease.

Language: Английский

Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association DOI Open Access
Saumya Das, Ravi V. Shah, Stefanie Dimmeler

et al.

Circulation Genomic and Precision Medicine, Journal Year: 2020, Volume and Issue: 13(4)

Published: June 29, 2020

The discovery that much of the non-protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion development tools technologies investigate these noncoding RNAs cardiovascular health. Furthermore, identifying for targeted therapeutics treat disease emerging area research. purpose this statement review existing literature, offer guidance on currently available study RNAs, identify areas unmet need.

Language: Английский

Citations

89
Long Non-Coding RNA and Breast Cancer DOI Creative Commons
Tianzhu Zhang, Hui Hu, Yan Ge

et al.

Technology in Cancer Research & Treatment, Journal Year: 2019, Volume and Issue: 18

Published: Jan. 1, 2019

Breast cancer, one of the most common diseases among women, is regarded as a heterogeneous and complicated disease that remains major public health concern. Recently, owing to development next-generation sequencing technologies, long non-coding RNAs have received extensive attention. Numerous studies reveal are playing important roles in tumor development. Although biological function molecular mechanisms remain enigmatic, recent researchers demonstrated an array express abnormally cancers, including breast cancer. Herein, we summarized latest literature about with particular focus on multiple regulatory regulate cell proliferation, invasion, metastasis, apoptosis.

Language: Английский

Citations

88
LOXL2 in cancer: regulation, downstream effectors and novel roles DOI
Bing Wen, Li‐Yan Xu, En‐Min Li

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2020, Volume and Issue: 1874(2), P. 188435 - 188435

Published: Sept. 22, 2020

Language: Английский

Citations

84
Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3 DOI Creative Commons

Panyang Zhang,

Yan Sun, Rui Peng

et al.

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(7)

Published: July 8, 2019

Abstract Diabetic nephropathy (DN) is one of the most significant complications diabetes and primary cause end-stage kidney disease. Cumulating evidence has shown that renal inflammation plays a role in development progression DN, but exact cellular mechanisms are unclear. Irregular expression long non-coding RNAs (lncRNAs) present many diseases, including DN. However, relationship between lncRNAs DN In this study, we identified differentially expressed using RNA-sequencing. Among these lncRNAs, seven DN-related vivo vitro quantitative real-time PCR. One lncRNA particular, Rpph1 (ribonuclease P RNA component H1), exhibited significantly increased expression. Further, over-expression or knockdown was found to regulate cell proliferation inflammatory cytokines mesangial cells (MCs). The results revealed directly interacts with factor galectin-3 (Gal-3). promoted through Gal-3/Mek/Erk signaling pathway MCs under low glucose conditions, while inhibited high conditions. These provide new insight into association during progression.

Language: Английский

Citations

79
Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype DOI Creative Commons

Laura Lecce,

Yang Xu,

Bhargavi V’Gangula

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(15)

Published: Aug. 1, 2021

Endothelial-mesenchymal transition (EndMT) is associated with various cardiovascular diseases and in particular atherosclerosis plaque instability. However, the molecular pathways that govern EndMT are poorly defined. Specifically, role of epigenetic factors histone deacetylases (HDACs) controlling atherosclerotic phenotype remains unclear. Here, we identified deacetylation, specifically mediated by HDAC9 (a class IIa HDAC), as playing an important both atherosclerosis. Using vitro models, found HDAC inhibition sustained expression endothelial proteins mitigated increase mesenchymal proteins, effectively blocking EndMT. Similarly, ex vivo genetic knockout Hdac9 cells prevented preserved a more endothelial-like phenotype. In vivo, atherosclerosis-prone mice endothelial-specific showed reduced significantly area. Furthermore, these displayed favorable phenotype, lipid content increased fibrous cap thickness. Together, findings indicate contributes to vascular pathology promoting Our study provides evidence for pathological link among EndMT, HDAC9, suggests targeting may be beneficial stabilization or slowing progression disease.

Language: Английский

Citations

69