Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure

2021 ◽  
Author(s):  
Zhenzhen Chen ◽  
Haizeng Zhang ◽  
Yingnan Bai ◽  
Changting Cui ◽  
Shuangyue Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Hydrostatic Pressure ◽  
Vascular Smooth Muscle ◽  
Single Cell ◽  
High Hydrostatic Pressure ◽  
Transcriptomic Analysis

scholarly journals In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model

2020 ◽  
Author(s):  
Shunji Kurokawa ◽  
Yoshihide Hashimoto ◽  
Seiichi Funamoto ◽  
Akitatsu Yamashita ◽  
Kazuhiro Yamazaki ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Hydrostatic Pressure ◽  
High Hydrostatic Pressure ◽  
Smooth Muscle Actin ◽  
Vascular Grafts ◽  
Graft Patency ◽  
Luminal Surface ◽  
Alpha Smooth Muscle Actin ◽  
Technical Improvement

ABSTRACTAutologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals potentially substitute for autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM) which would be feasible for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Surgical procedure not to damage luminal surface of the grafts from drying significantly increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. Luminal surface of grafts was thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.

In vitro reactivity of ventral aorta to acetylcholine and noradrenaline in yellow freshwater eel (Anguilla anguilla L.) acclimatized to 10.1 MPa hydrostatic pressure

2000 ◽  
Vol 78 (11) ◽  
pp. 897-903 ◽  
Author(s):  
François Guerrero ◽  
Mickael Theron ◽  
Philippe Sebert
Keyword(s):  
Smooth Muscle ◽  
Hydrostatic Pressure ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Anguilla Anguilla ◽  
Dry Weight ◽  
Isometric Tension ◽  
Response Curves

We examined in vitro vascular reactivity of eels previously acclimatized to 10.1 MPa hydrostatic pressure (HP) for 21 days. The isometric tension developed by ventral aortic rings was measured at atmospheric pressure. Dose-response curves for either acetylcholine (ACh) or noradrenaline (NA), as well as contractions evoked by 80 mM K+, were compared with time-matched experiments conducted on rings obtained from control eels. Results showed that neither the optimal tension nor the maximal force of the K+-evoked contraction were significantly modified, suggesting that acclimatization to high HP did not change the vascular smooth muscle contractile machinery. The dose-response curve to ACh was not significantly changed. Conversely, although NA always relaxed aortic rings, the response of acclimatized eels was significantly reduced over the entire range of the agonist concentration tested (10-8 to 10-3 M), except for the lowest one (10-9 M). The maximal amplitude of the NA-induced relaxation was significantly reduced in aortic rings from acclimatized eels as compared with non-acclimatized samples (339.3 ± 86.5 vs. 744.3 ± 72.1 mg·mg-1 dry weight, P < 0.005). Our results suggest that acclimatization to high HP could selectively alter the control of vascular tone by catecholamines.Key words: fish, high pressure, vascular smooth muscle, adrenoceptors, cholinergic receptors.

scholarly journals Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1    

2020 ◽  
Author(s):  
Weiyi Qian ◽  
Tarik Hadi ◽  
Xiao Ma ◽  
Michele Silvestro ◽  
Cristobal Rivera ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Membrane ◽  
Vascular Smooth Muscle ◽  
Single Cell ◽  
Vascular Wall ◽  
Aortic Aneurysms ◽  
Theoretical Modelling ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
Novel Target

Abstract Mechanical overload of the vascular wall is a pathological hallmark of life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at the unicellular level of vascular smooth muscle cells (VSMC) in AAA is undefined. Here, we combined novel ultrasound tweezers-based micromechancal system and single-cell RNA sequencing to map defective mechano-phenotype signature of VSMC niched in AAA. VSMC gradually adopted a mechanically solid-like state by upregulating cytoskeleton (CSK) crosslinker, α-actinin2, which stiffened VSMC cell membrane thereby directly powering the activity of mechano-sensory ion channel Piezo1 during AAA development. Theoretical modelling predicted that in AAA, such CSK alterations fueled cell membrane tension thereby blocking physiological mechanoallostatic responses of VSMC. Single-cell mechanical measurements and frequency spectrum analysis validated the mechanosensation deficiency in VSMC during AAA development. Our findings demonstrate that deviations of mechanosensation behaviors of VSMC is detrimental for AAA and identifies Piezo1 as a novel target to curb AAA onset.

scholarly journals Inflammatory Cells Accelerated Carotid Artery Calcification via MMP9: Evidences From Single-Cell Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaobing Liang ◽  
Wanbing He ◽  
Hua Zhang ◽  
Dongling Luo ◽  
Zhengzhipeng Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Single Cell ◽  
Vascular Smooth Muscle Cells ◽  
Interaction Analysis ◽  
Muscle Cells ◽  
Mmp9 Expression ◽  
Phenotypic Transformation

Background: Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. However, the implications and potential mechanisms for VSMCs phenotypic transition remain unknown.Methods: To study the transformation of vascular smooth muscle cells (VSMCs) in the calcification early period, we analyzed single-cell sequencing data from carotid artery calcified core and paracellular tissue, based on the results of enrichment analysis and protein-protein interaction analysis. Upstream transcription factors were tracked and finally the results were validated using the MESA database.Results: We successfully identified a subpopulation of inflammatory macrophage-like VSMCs and determined that MMP9 is an important factor in the phenotypic transformation of VSMCs. We found that RELA regulates MMP9 expression and that knockdown of RELA attenuated MMP9 expression and reduced the expression of BMP2 and the macrophage marker LGALS3 in vascular smooth muscle in inflammatory states, while serum levels of MMP9 correlated significantly with the inflammatory response.Conclusion: This study reveals that the phenotypic transformation of VSMCs can be regulated by modulating MMP9, providing a new idea for the early treatment of VC.

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

Sign in / Sign up

Export Citation Format

Share Document