scholarly journals Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4)

2021 ◽  
Author(s):  
Carmen Yap ◽  
Arnout Mieremet ◽  
Carlie J.M. de Vries ◽  
Dimitra Micha ◽  
Vivian de Waard
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Disease ◽  
Single Cell ◽  
Vascular Smooth Muscle Cells ◽  
Vessel Wall ◽  
Single Cell Rna Sequencing ◽  
Sequencing Studies ◽  
Phenotype Switching

Multiple layers of vascular smooth muscle cells (vSMCs) are present in blood vessels forming the media of the vessel wall. vSMCs provide a vessel wall structure, enabling it to contract and relax, thus modulating blood flow. They also play a crucial role in the development of vascular diseases, such as atherosclerosis and aortic aneurysm formation. vSMCs display a remarkable high degree of plasticity. At present, the number of different vSMC phenotypes has only partially been characterized. By mapping vSMC phenotypes in detail and identifying triggers for phenotype switching, the relevance of the different phenotypes in vascular disease may be identified. Up until recently, vSMCs were classified as either contractile or dedifferentiated (ie, synthetic). However, single-cell RNA sequencing studies revealed such dedifferentiated arterial vSMCs to be highly diverse. Currently, no consensus exist about the number of vSMC phenotypes. Therefore, we reviewed the data from relevant single-cell RNA sequencing studies, and classified a total of 6 vSMC phenotypes. The central dedifferentiated vSMC type that we classified is the mesenchymal-like phenotype. Mesenchymal-like vSMCs subsequently seem to differentiate into fibroblast-like, macrophage-like, osteogenic-like, and adipocyte-like vSMCs, which contribute differentially to vascular disease. This phenotype switching between vSMCs requires the transcription factor KLF4 (Krüppel-like factor 4). Here, we performed an integrated analysis of the data about the recently identified vSMC phenotypes, their associated gene expression profiles, and previous vSMC knowledge to better understand the role of vSMC phenotype transitions in vascular pathology.

scholarly journals Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium

2020 ◽  
Author(s):  
PM Kirkwood ◽  
DA Gibson ◽  
JR Smith ◽  
JR Wilson-Kanamori ◽  
O Kelepouri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Vascular Smooth Muscle Cells ◽  
Mesenchymal Cell ◽  
Muscle Cells ◽  
Perivascular Niche ◽  
Single Cell Rna Sequencing

AbstractThe endometrium is a dynamic tissue that exhibits remarkable resilience to repeated episodes of differentiation, breakdown, regeneration and remodelling. Endometrial physiology relies on a complex interplay between the stromal and epithelial compartments with the former containing a mixture of fibroblasts, vascular and immune cells. There is evidence for rare populations of putative mesenchymal progenitor cells located in the perivascular niche of human endometrium, but the existence of an equivalent cell population in mouse is unclear.In the current study we used the Pdgfrb-BAC-eGFP transgenic reporter mouse in combination with bulk and single cell RNA sequencing (scRNAseq) to redefine the endometrial mesenchyme. Contrary to previous reports we show that CD146 is expressed in both PDGFRβ+ perivascular cells as well as CD31+ endothelial cells. Bulk RNAseq revealed cells in the perivascular niche which express high levels of Pdgfrb as well as genes previously identified in pericytes and/or vascular smooth muscle cells (Acta2, Myh11, Olfr78, Cspg4, Rgs4, Rgs5, Kcnj8, Abcc9). scRNAseq identified five subpopulations of cells including closely related pericytes/vascular smooth muscle cells and three subpopulations of fibroblasts. All three fibroblast populations were PDGFRα+/CD34+ but were distinct in their expression of Spon2/Angptl7 (fibroblast 1), Smoc2/Rgs2 (fibroblast 2) and Clec3b/Col14a1/Mmp3 (fibroblast 3), with potential functions in regulation of immune responses, response to wounding and organisation of extracellular matrix respectively.In conclusion, these data are the first to provide a single cell atlas of the mesenchymal cell landscape in mouse endometrium. By identifying novel markers for subpopulations of mesenchymal cells we can use mouse models investigate their contribution to endometrial function, compare with other tissues and apply these findings to further our understanding of human endometrium.HighlightsGFP expression in the mouse endometrium, under the control of the Pdgfrb promoter, is restricted to two cell populations based on the intensity of GFP with GFPbright cells close to the vasculatureSingle cell RNAseq identified five subpopulations of GFP+ mesenchymal cells: pericytes, vascular smooth muscle cells (vSMC) and three closely related but distinct populations of fibroblastsBioinformatics revealed that pericytes and vSMC share functions associated with the circulatory system, actin-filament process and cell adhesion, and an apparent role for pericytes in smooth muscle cell migration and response to interferonsComparisons between the fibroblast subpopulations suggest distinct roles in regulation of immune response, response to wound healing and collagen organisation.Graphical Abstract

Matrix Gla Protein Synthesis and Gamma-carboxylation in the Aortic Vessel Wall and Proliferating Vascular Smooth Muscle Cells

1999 ◽  
Vol 82 (12) ◽  
pp. 1764-1767 ◽  
Author(s):  
Dean Cain ◽  
David Sane ◽  
Reidar Wallin
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vitamin K ◽  
Vessel Wall ◽  
Arterial Wall ◽  
Muscle Cells ◽  
Matrix Gla Protein ◽  
Dt Diaphorase

SummaryMatrix GLA protein (MGP) is an inhibitor of calcification in the arterial wall and its activity is dependent upon vitamin K-dependent γ-carboxylation. This modification is carried out by a warfarin sensitive enzyme system that converts specific Glu residues to γ-carboxyglutamic acid (GLA) residues. Recent studies have demonstrated that the γ-carboxylation system in the arterial wall, in contrast to that in the liver, is unable to use vitamin K as an antidote to warfarin.By use of immunohistochemistry we demonstrate that MGP is expressed in the arterial wall and immunocytochemistry localized the MGP precursors to the endoplasmic reticulum in vascular smooth muscle cells. Resting smooth vascular muscle cells in the aortic wall and proliferating cells from explants of the aorta have all the enzymes needed for γ-carboxylation of MGP. However, when compared to the liver system, expression of the enzymes of the γ-carboxylation system in vascular smooth muscle cells is different. Of particular interest is the finding that the specific activity of the warfarin sensitive enzyme vitamin K epoxide reductase is 3-fold higher in vascular smooth muscle cells than in liver. DT-diaphorase, which catalyses the antidotal pathway for vitamin K reduction in liver, is 100-fold less active in resting vascular smooth muscle cells than in liver. Data obtained from an in vitro γ-carboxylation system suggest that the antidotal pathway catalyzed by DT-diaphorase in the vessel wall is unable to provide the carboxylase with enough reduced vitamin K to trigger γ-carboxylation of MGP. This finding provides an explanation to the inability of vitamin K to work as an antidote to warfarin intoxication of the arterial wall. Therefore the vitamin K dependent γ-carboxylation system in the arterial wall share a common feature with the system in bone cells by being unable to utilize vitamin K as an antidote.

Defective autophagy in vascular smooth muscle cells increases passive stiffness of the mouse aortic vessel wall

2020 ◽  
Vol 472 (8) ◽  
pp. 1031-1040 ◽  
Author(s):  
Dorien G. De Munck ◽  
Arthur J.A. Leloup ◽  
Guido R. Y. De Meyer ◽  
Wim Martinet ◽  
Paul Fransen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vessel Wall ◽  
Muscle Cells ◽  
Passive Stiffness

scholarly journals Prostaglandin E1 Inhibited Diabetes-Induced Phenotypic Switching of Vascular Smooth Muscle Cells Through Activating Autophagy

2018 ◽  
Vol 50 (2) ◽  
pp. 745-756 ◽  
Author(s):  
Xing-Rong An ◽  
Xin Li ◽  
Wei Wei ◽  
Xiao-Xue Li ◽  
Ming Xu
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Prostaglandin E1 ◽  
Vascular Complications ◽  
Muscle Cells ◽  
In Vivo Study ◽  
Phenotype Switching

Background/Aims: The phenotype switching of vascular smooth muscle cells (VSMCs) was associated with the onset or progression of the atherogenic process in type 2 diabetes mellitus (T2DM). Alprostadil (Prostaglandin E1, PGE1) as a bioactive drug had a protective effect on vascular function. However, it is unknown whether PGE1 inhibited the phenotype switching in VSMCs via autophagy, which played a protective role in the vascular complications of diabetes. Methods: The phenotype switching was induced by high glucose (HG, 25mM) in VSMCs, the protein expression was measured by western blot analysis and immunofluorescent staining. In vivo study, vascular lesion and dysfunction were produced in the rats fed with high fat diet (HFD) combined with low dose streptozotocin (STZ) administration. Results: The decrease of α-SMA and the increase of vimentin, collagen I and proliferating cell nuclear antigen (PCNA) were found in HG-treated VSMCs. Along with more abundance of p62, autophagy markers LC3B and Beclin-1 significantly decreased in VSMCs exposed to HG. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy activator rapamycin and was dramatically counteracted by 3-methyladenine, an autophagy inhibitor. Furthermore, PGE1 suppressed the phosphorylation of AKT and mTOR, which negatively regulated autophagy level in VSMCs. In vivo study, PGE1 remarkably improved the endothelium-independent contraction of thoracic aorta and restored the expression of α-SMA, osteopontin, LC3B, phosphorylated mTOR in the artery media of T2DM rats. Conclusion: These results demonstrated that PGE1 maintained the phenotype of VSMCs via the AKT/mTOR-dependent autophagy, which prevented diabetes-induced vascular complications.

scholarly journals Panax notoginsengSaponins Attenuate Phenotype Switching of Vascular Smooth Muscle Cells Induced by Notch3 Silencing

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Nan Liu ◽  
Dazhi Shan ◽  
Ying Li ◽  
Hui Chen ◽  
Yonghong Gao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Panax Notoginseng ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Dependent Manner ◽  
Phenotype Switching ◽  
Dose Dependent

Panax notoginsengsaponins (PNS) could maintain vascular smooth muscle cells (VSMCs) in stable phenotypes so as to keep blood vessel elasticity as well as prevent failing in endovascular treatment with stent. Downregulation of Notch3 expression in VSMCs could influence the phenotype of VSMCs under pathologic status. However, whether PNS is able to attenuate the Notch3 silencing induced phenotype switching of VSMCs remains poorly understood. Primary human VSMCs were transfected with a plasmid containing a small interfering RNA (siRNA) against Notch3 and then exposed to different doses of PNS. The control groups included cells not receiving any treatment and cells transfected with a control siRNA. Phenotypic switching was evaluated by observing cell morphology with confocal microscopy, as well as examiningα-SM-actin, SM22α, and OPN using Western blot. Downregulated Notch3 with a siRNA induced apparent phenotype switching, as reflected by morphologic changes, decreased expression ofα-SM-actin and SM22αand increased expression of OPN. These changes were inhibited by PNS in a dose-dependent manner. The phenotype switching of VSMCs induced by Notch3 knockdown could be inhibited by PNS in a dose-dependent manner. Our study provided new evidence for searching effective drug for amending stability of atherosclerotic disease.

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