Abstract 241: An Increased Response to Injury by Smooth Muscle Cells of Human Veins at Valve Sites

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Lihua Chen ◽  
Kevin Xiong ◽  
Yukihiro Saito ◽  
Nobuyoshi Azuma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Global Gene Expression ◽  
Muscle Cells ◽  
Differentially Expressed ◽  
Tissue Explants ◽  
Venous Valves ◽  
Cell Counts ◽  
And Migration

Objective: Venous valves are prone to injury, thrombosis and fibrosis. We compared the behavior and gene expression of smooth muscle cells (SMCs) in the valve sinus vs non-valve sites to elucidate biological differences associated with vein valves. Methods: SMC migration was measured using 2.5 mm 2 explants of the intima/media of valve sinus segments (without valve leaflets) vs. non-valve segments of human saphenous veins. Proliferation and death of SMCs was determined by staining for Ki67 and TUNEL, respectively. Proliferation and migration of passaged valve vs non-valve SMCs was determined by cell counts and using microchemotaxis chambers. Global gene expression in valve vs non-valve intima/media was determined by RNA-Seq. Results: Valve SMCs demonstrated greater proliferation within tissue explants compared to non-valve SMCs (19.3±5.4% vs. 6.8±2.0% Ki67 positive nuclei at 4 days, respectively; mean ± SEM, 5 veins; P<.05). This was also true for migration (18.2±2.7 vs. 7.5±3.0 migrated SMCs/explant at 6 days, respectively; 24 veins, 15 explants/vein; P<.0001). Cell death was not different (39.6±16.1% vs. 41.5±16.0% TUNEL positive cells, respectively, at 4 days, 5 veins). Cultured valve SMCs also proliferated faster than non-valve SMCs in response to PDGF-BB (2.9±0.2 vs. 2.1±0.2 fold of control, respectively; P<.001; N=5 vein’s paired cells). This was also true for migration (6.5±1.2 vs. 4.4±0.8 fold of control, respectively; P<.001; N=7 vein’s paired cells). Blockade of FGF2 inhibited the increased responses of valve SMCs, but had no effect on non-valve SMCs. Exogenous FGF2 increased migration of valve, but not non-valve SMCs. Unexpectedly, blockade of FGF2 did not block migration of valve or non-valve SMCs from tissue explants. 37 genes were differentially expressed by valve compared to non-valve intimal/medial tissue (11 veins). Conclusions: Valve, compared to non-valve, SMCs have greater rates of migration and proliferation, which may in part explain the propensity for pathological lesion formation in valves. While FGF2 mediates these effects in cultured SMCs, the mediators of these stimulatory effects in valve wall tissue remain unidentified. Here, the newly identified differentially expressed genes may play a role.

scholarly journals GRIA2/ENPP3 Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells in the Restenosis Process Post-PTA in Lower Extremity Arteries

2021 ◽  
Vol 12 ◽  
Author(s):  
Mi Zhou ◽  
Lixing Qi ◽  
Yongquan Gu
Keyword(s):  
Smooth Muscle ◽  
Lower Extremity ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Enrichment Analysis ◽  
Muscle Cells ◽  
Differentially Expressed ◽  
And Migration ◽  
Proliferation And Migration

Restenosis is the main restriction on the long-term efficacy of percutaneous transluminal angioplasty (PTA) therapy for peripheral artery disease (PAD). Interventions to prevent restenosis are poor, and the exact mechanism is unclear. Here, we aimed to elucidate the role of GRIA2 in the restenosis process post-PTA in lower extremity arteries. We searched the differentially expressed genes (DEGs) between atherosclerotic and restenotic artery plaques in the Gene Expression Omnibus (GEO), and five DEGs were identified. Combined with Gene Ontology (GO) enrichment analysis, GRIA2 was significantly correlated with the restenosis process. Tissue samples were used to examine GRIA2 expression by immunofluorescence staining of atherosclerotic and restenotic artery plaques. The regulation of GRIA2 in vascular smooth muscle cells (VSMCs) was confirmed by lentiviral transfection. Overexpression of GRIA2 promoted the proliferation and migration of VSMCs. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network, a strong connection between ENPP3 and GRIA2 was discovered. In vitro results showed that the high expression of GRIA2 in VSMCs enhanced the expression of ENPP3, while downregulation of GRIA2 downregulated ENPP3. GRIA2 is highly differentially expressed in restenotic arterial plaques, promoting the proliferation and migration of VSMCs through upregulation of ENPP3. These discoveries will help us to obtain a better understanding of restenosis in lower extremity arteries.

Gene Expression in Atherogenesis

2001 ◽  
Vol 86 (07) ◽  
pp. 404-412 ◽  
Author(s):  
Houshang Monajemi ◽  
E. Karin Arkenbout ◽  
Hans Pannekoek
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Transcription Factors ◽  
Smooth Muscle Cells ◽  
Differential Gene Expression ◽  
New Technologies ◽  
Muscle Cells ◽  
Differentially Expressed ◽  
Differential Gene

SummaryIt is conceivable that the extent and spatio-temperal expression of dozens or even a few hundred genes are significantly altered during the development and progression of atherosclerosis as compared to normal circumstances. Differential gene expression in vascular cells and in blood cells, due to gene-gene and gene-environment interactions can be considered the molecular basis for this disease. To comprehend the coherence of the complex genetic response to systemic and local atherosclerotic challenges, one needs accessible high through-put technologies to analyze a panel of differentially expressed genes and to describe the interactions between and among their gene products. Fortunately, new technologies have been developed which allow a complete inventory of differential gene expression, i.e. DD/RT-PCR, SAGE and DNA micro-array. The initial data on the application of these technologies in cardiovascular research are now being reported. This review summarizes a number of key observations. Special attention is paid to a few central transcription factors which are differentially expressed in endothelial cells, smooth muscle cells or monocytes/ macrophages. Recent data on the role of nuclear factor- B (NF-κB) and peroxisome proliferation-activating receptors (PPARs) are discussed. Like the PPARs, the NGFI-B subfamily of orphan receptors (TR3, MINOR and NOT) also belongs to the steroid/thryroid hormone receptor superfamily of transcription factors. We report that this subfamily is specifically induced in a sub-population of neointimal smooth muscle cells. Furthermore, intriguing new data implicating the Sp/XKLF family of transcription factors in cell-cell communication and maintenance of the atherogenic phenotype are mentioned. A member of the Sp/XKLF family, the shear stress-regulated lung Krüppel-like factor (LKLF) is speculated to be instrumental for the communication between endothelial cells and smooth muscle cells. Taken together, the expectation is that the fundamental knowledge obtained on atherogenesis and the data that will be acquired during the coming decade with the new, powerful high through-put methodologies will lead to novel modalities to treat patients suffering from cardiovascular disease. In view of the phenotypic changes of vascular and blood-borne cells during atherogenesis, therapeutic interventions likely will focus on reversal of an acquired phenotype by gene therapy approach or by using specific drugs which interfere with aberrant gene expression.

scholarly journals Transcriptomic sequencing reveals diverse adaptive gene expression responses of human vascular smooth muscle cells to nitro-conjugated linoleic acid

2018 ◽  
Vol 50 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Shengdi Li ◽  
Ziyi Chang ◽  
Tianqing Zhu ◽  
Luis Villacorta ◽  
Yixue Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Smooth Muscle Cells ◽  
Conjugated Linoleic Acid ◽  
Differentially Expressed Genes ◽  
Muscle Cells ◽  
Functional Enrichment ◽  
Differentially Expressed

Nitro-conjugated linoleic acid (NO2-CLA) is formed by metabolic and inflammatory reactions of nitric oxide and nitrite, and represents the most abundant nitro-fatty acid species in humans. These electrophilic fatty acid nitroalkene derivatives mediate pleiotropic cell signaling responses. Here, we report a systematic approach to investigate the effect of NO2-CLA on human coronary artery smooth muscle cells (hCASMC), based on the RNA-Seq and bioinformatics analysis. There were extensive differentially expressed genes in NO2-CLA vs. control (510) and NO2-CLA vs. CLA (272) treatment groups, respectively. Notably, only minimal alterations were observed in CLA vs. control conditions, indicating that the electrophilic character of NO2-CLA is requited to induce differential gene expression responses independently from native CLA. Functional enrichment analysis of differentially expressed genes reveals multiple cellular processes to be affected under NO2-CLA treatment, including cell proliferation, lipid metabolism, antioxidant and inflammatory-related gene expression responses. These findings reveal that nitro-fatty acid derivatives such as NO2-CLA regulate a broad array of adaptive gene expression responses by hCASMC.

scholarly journals LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yaqing Zhou ◽  
Sheng Zhang ◽  
Wenfeng Ji ◽  
Xiongkang Gan ◽  
Lei Hua ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Rna Sequencing ◽  
Target Genes ◽  
Muscle Cells ◽  
Differentially Expressed ◽  
Human Coronary Artery ◽  
And Migration ◽  
Proliferation And Migration

We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&amp;E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. GON4L was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA–miRNA–mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.

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