scholarly journals RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

2021 ◽  
Vol 12 ◽  
Author(s):  
Yohei Mineharu ◽  
Susumu Miyamoto
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Moyamoya Disease ◽  
Fibrous Tissue ◽  
Muscle Cells ◽  
Pulmonary Artery Hypertension ◽  
Large Artery ◽  
Vascular Protection ◽  
Vascular Stability ◽  
Artery Disease

Moyamoya disease is an idiopathic chronically progressive cerebrovascular disease, which causes both ischemic and hemorrhagic stroke. Genetic studies identified RNF213/Mysterin and GUCY1A3 as disease-causing genes. They were also known to be associated with non-moyamoya intracranial large artery disease, coronary artery disease and pulmonary artery hypertension. This review focused on these two molecules and their strong linker, calcineurin/NFAT signaling and caveolin to understand the pathophysiology of moyamoya disease and related vascular diseases. They are important regulators of lipid metabolism especially lipotoxicity, NF-κB mediated inflammation, and nitric oxide-mediated vascular protection. Although intimal thickening with fibrosis and damaged vascular smooth muscle cells are the distinguishing features of moyamoya disease, origin of the fibrous tissue and the mechanism of smooth muscle cell damages remains not fully elucidated. Endothelial cells and smooth muscle cells have long been a focus of interest, but other vascular components such as immune cells and extracellular matrix also need to be investigated in future studies. Molecular research on moyamoya disease would give us a clue to understand the mechanism preserving vascular stability.

Abstract 273: P2Y2 Receptor-Mediated Lymphotoxin-α Secretion Regulates ICAM-1 Expression in Smooth Muscle Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Cheikh Seye ◽  
Wilbert Derbigny ◽  
Shaomin Qian
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Protein Transport ◽  
Brefeldin A ◽  
Muscle Cells ◽  
Secretory Vesicle ◽  
Actin Binding ◽  
Filamin A ◽  
Artery Disease ◽  
Lymphotoxin Α

Rationale: Single nucleotide polymorphism (SNP) in the LGASL2 galectin-2 (Gal-2) gene leads to altered secretion of lymphotoxin-α (LT-α) and is associated with coronary artery disease. Objective:Our aim was to determine whether factors other than genetic variations in LGASL2 regulate LT-α release and to define the role of this pro-inflammatory in vascular smooth muscle cells (SMC). Methods and results: The proinflammatory cytokine lymphotoxin-alpha (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in VSMC are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y 2 nucleotide receptor (P2Y 2 R) agonist UTP stimulates a strong and sustained release of LTA from wild-type but not P2Y 2 R -/- SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Re-introduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found UTP-stimulated LTA secretion is not sensitive to brefeldin A (BFA), which blocks the formation of vesicles involved in protein transport from the ER to the Golgi apparatus, suggesting that P2Y 2 R/filamin-mediated secretion of LTA is independent of the ER/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y 2 R deficient in LTA secretion. Conclusion: These data suggest that P2Y 2 R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on VSMC.

scholarly journals TGFβ, smooth muscle cells and coronary artery disease: a review

2019 ◽  
Vol 53 ◽  
pp. 90-101 ◽  
Author(s):  
Emma L. Low ◽  
Andrew H. Baker ◽  
Angela C. Bradshaw
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Artery Disease

scholarly journals MicroRNA regulation of BMP signaling; cross-talk between endothelium and vascular smooth muscle cells

2018 ◽  
Author(s):  
Charlene Watterston ◽  
Lei Zeng ◽  
Abidemi Onabadejo ◽  
Sarah J Childs
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Function ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Vascular Stability ◽  
Bmp Signalling

AbstractVascular smooth muscle cells (vSMC) are essential to the integrity of blood vessels, and therefore an attractive target of therapeutics aimed at improving vascular function. Smooth muscle cells are one of the few cell types that maintain plasticity and can switch phenotypes from differentiated (contractile) to de-differentiated (synthetic) and vice versa. As small regulatory transcripts, miRNAs act as genetic ‘fine tuners’ of posttranscriptional events and can act as genetic switches promoting phenotypic switching. The microRNAmiR26atargets the BMP signalling effector,smad1. We show that loss ofmiR26leads to hemorrhage (a loss of vascular stability)in vivo, suggesting altered vascular differentiation. Reduction inmiR26alevels increasessmad1mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression ofsmad1also leads to hemorrhage and that normalization of Smad1 levels through double knockdown ofmiR26andsmad1rescues hemorrhage suggesting a direct relationship betweenmiR26andsmad1and vascular stability. Using a BMP genetic reporter and pSmad1 staining we show that the effect ofmiR26on vascular instability is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss ofmiR26results in an increase inacta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Taken together our data suggests thatmiR26modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data also suggests that crosstalk from BMP-responsive endothelium to smooth muscle is important for its differentiation.

scholarly journals The Emerging Role of Long Non-coding RNAs and Circular RNAs in Coronary Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Mahdi Gholipour ◽  
Mohammad Taheri
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Circular Rnas ◽  
Numerous Cell ◽  
Non Coding Rnas ◽  
Artery Disease

Coronary artery disease (CAD) is a common disorder caused by atherosclerotic processes in the coronary arteries. This condition results from abnormal interactions between numerous cell types in the artery walls. The main participating factors in this process are accumulation of lipid deposits, endothelial cell dysfunction, macrophage induction, and changes in smooth muscle cells. Several lines of evidence underscore participation of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the pathogenesis of CAD. Several lncRNAs such as H19, ANRIL, MIAT, lnc-DC, IFNG-AS1, and LEF1-AS1 have been shown to be up-regulated in the biological materials obtained from CAD patients. On the other hand, Gas5, Chast, HULC, DICER1-AS1, and MEG3 have been down-regulated in CAD patients. Meanwhile, a number of circRNAs have been demonstrated to influence function of endothelial cells or vascular smooth muscle cells, thus contributing to the pathogenesis of CAD. In the current review, we summarize the function of lncRNAs and circRNAs in the development and progression of CAD.

Role of the signal transducer and activator of transcription 3 protein in the proliferation of vascular smooth muscle cells

Vascular ◽  
2020 ◽  
Vol 28 (6) ◽  
pp. 821-828
Author(s):  
Hong-Xia Tang ◽  
Xu-Ping Qin ◽  
Jie Li
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Signal Transducer ◽  
Vsmc Proliferation ◽  
Stat3 Signaling Pathway ◽  
Artery Disease ◽  
Transcription 3

Objectives Cardiovascular disease (CVD) remains the primary cause of morbidity and mortality worldwide. The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of CVD. The functional and phenotypic changes in vascular cells are mediated by complex signaling cascades that initiate and control genetic reprogramming. Many studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) regulates a diverse array of functions relevant to atherosclerosis. Methods In this review, we summarize the studies on the STAT3-mediated proliferation of VSMCs and subsequent CVDs such as hypertension, atherosclerosis, stroke, coronary artery disease, and myocardial infarction. Furthermore, we describe the general background of STAT3, its structure, function and regulation as well as the STAT3 signaling pathway. Finally, we highlight some potential issues and propose some solutions to these issues. Results and conclusions: STAT3 activation promotes the proliferation of VSMCs by regulating the transcription of genes. Studying the mechanism of VSMC proliferation induced by the STAT3 pathway is valuable for finding therapeutic targets for CVD.

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