scholarly journals Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 593
Author(s):  
Alexander Lin ◽  
Niridu Jude Peiris ◽  
Harkirat Dhaliwal ◽  
Maria Hakim ◽  
Weizhen Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neurodegenerative Diseases ◽  
Structural Integrity ◽  
Vascular System ◽  
Vascular Wall ◽  
Cell Plasticity ◽  
Mural Cell ◽  
Mural Cells ◽  
Heterogenous Population

Mural cells collectively refer to the smooth muscle cells and pericytes of the vasculature. This heterogenous population of cells play a crucial role in the regulation of blood pressure, distribution, and the structural integrity of the vascular wall. As such, dysfunction of mural cells can lead to the pathogenesis and progression of a number of diseases pertaining to the vascular system. Cardiovascular diseases, particularly atherosclerosis, are perhaps the most well-described mural cell-centric case. For instance, atherosclerotic plaques are most often described as being composed of a proliferative smooth muscle cap accompanied by a necrotic core. More recently, the role of dysfunctional mural cells in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, is being recognized. In this review, we begin with an exploration of the mechanisms underlying atherosclerosis and neurodegenerative diseases, such as mural cell plasticity. Next, we highlight a selection of signaling pathways (PDGF, Notch and inflammatory signaling) that are conserved across both diseases. We propose that conserved mural cell signaling mechanisms can be exploited for the identification or development of dual-pronged therapeutics that impart both cardio- and neuroprotective qualities.

scholarly journals The Role of Uridine Adenosine Tetraphosphate in the Vascular System

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Rita C. Tostes ◽  
R. Clinton Webb
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Vascular Function ◽  
Purinergic Receptors ◽  
Potential Role ◽  
Vascular System

The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up4A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up4A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up4A modulates vascular function by actions on endothelial and smooth muscle cells. In this paper, we discuss the effects of Up4A on vascular function and a potential role for Up4A in cardiovascular diseases.

Endothelial and Smooth Muscle Cells as Antagonists in Vascular Fibrinoysis

1975 ◽  
Author(s):  
V. Noordhoek Hegt
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Vascular System ◽  
Muscle Cells ◽  
Vascular Wall ◽  
Vasa Vasorum ◽  
Slide Technique

Endothelial plasminogen activator activity in different types of human blood vessels obtained from fifty necropsies and thirty-five biopsies was detected and localized by means of plasminogen-rich fibrin slides. Great differences in endothelial activator activity were found along and across (vasa vasorum) the wall of the human vascular system.The same blood vessels were simultaneously investigated by a modified fibrin slide technique using plasminogen-free fibrin slides covered by plasmin to detect and localize inhibition of fibrinolysis in the vascular wall. The great variation in plasmin inhibition in different vessels revealed by this “fibrin slide sandwich technique” appeared to be closely associated with the localization and number of smooth muscle cells present in the walls of the vascular system. Strong plasmin inhibition was generally found at sites which showed no activator activity with the regular fibrin slide technique, while areas with a high endothelial fibrinolytic activity mostly revealed no inhibitory capacity.These results indicate that much of the variation in endothelial fibrinolytic activity on fibrin slides is due to inhibitory effects from the surrounding smooth muscle cells rather than to variability in the plasminogen activator content of the endothelium itself.

scholarly journals Organizational Hierarchy and Structural Diversity of Microvascular Pericytes in Adult Mouse Cortex

2017 ◽  
Author(s):  
Roger I. Grant ◽  
David A. Hartmann ◽  
Robert G. Underly ◽  
Andrée-Anne Berthiaume ◽  
Narayan R. Bhat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Cell Types ◽  
Mural Cell ◽  
Mural Cells ◽  
Mouse Cortex ◽  
Transitional Cells ◽  
Brain Microvasculature

ABSTRACTSmooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3047-3055 ◽  
Author(s):  
M. Hellstrom ◽  
M. Kal n ◽  
P. Lindahl ◽  
A. Abramsson ◽  
C. Betsholtz
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular System ◽  
Muscle Cells ◽  
Brdu Labeling ◽  
Pdgfr Beta

Development of a vascular system involves the assembly of two principal cell types - endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) - into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B−/− and PDGFR-beta−/− embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B−/− embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-beta-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.

scholarly journals Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1260-1266 ◽  
Author(s):  
Hanako Kobayashi ◽  
Laura M. DeBusk ◽  
Yael O. Babichev ◽  
Daniel J. Dumont ◽  
Pengnian Charles Lin
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Mural Cell ◽  
Mural Cells ◽  
Hepatocyte Growth ◽  
Vascular Maturation

Abstract Communication between endothelial cells (ECs) and mural cells is critical in vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during vascular maturation. However, the molecular mechanism is unclear. We used microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation. We confirmed this finding by Northern blot and Western blot analyses in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay. Addition of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment, indicating that the induction of SMC migration by Ang1 was caused by the increase of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced HGF production and Ang1-induced SMC migration. Finally, we showed that deletion of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and suggest that a delicate balance between Ang1 and Ang2 is critical in this process.

scholarly journals Heterogeneous pdgfrβ+ cells regulate coronary vessel development and revascularization during heart regeneration

2021 ◽  
Author(s):  
Subir Kapuria ◽  
Haipeng Bai ◽  
Juancarlos Fierros ◽  
Ying Huang ◽  
Feiyang Ma ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Arteries ◽  
Heart Development ◽  
Coronary Vessel ◽  
Heart Regeneration ◽  
Atrioventricular Canal ◽  
Mural Cell ◽  
Mural Cells ◽  
Vessel Development ◽  
Zebrafish Heart

ABSTRACTEndothelial cells emerge from the atrioventricular canal (AVC) to form nascent coronary blood vessels in the juvenile zebrafish heart. We found that pdgfrβ is first expressed in the epicardium around the AVC and later becomes localized mainly in the mural cells. pdgfrβ mutant fish display severe defects in mural cell recruitment and coronary vessel development. pdgfrβ+ mural cells are heterogeneous and those associated with coronary arteries also express cxcl12b. Mural cells positive for both pdgfrβ and cxcl12b transgenic reporters had elevated expression of smooth muscle cell genes. Interestingly, these mural cells were associated with coronary arteries even in the absence of Pdgfrβ, although smooth muscle gene expression was downregulated in these cells. We found that pdgfrβ expression dynamically changes in the epicardium derived cells, which we found to be a heterogeneous population. mdka was identified as a gene upregulated in subpopulations of pdgfrβ+ cells during heart regeneration. However, pdgfrβ but not mdka mutants showed defects in heart regeneration. Our results demonstrated that pdgfrβ+ cells and Pdgfrβ signaling are essential for coronary development and heart regeneration.SUMMARY STATEMENTHeterogeneous pdgfrβ positive cells are present in developing and regenerating zebrafish hearts and are required for development of mural cells and their association with the nascent coronary vessels during zebrafish heart development and regeneration.

scholarly journals Zebrafish Vascular Mural Cell Biology: Recent Advances, Development, and Functions

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1041
Author(s):  
Koji Ando ◽  
Tomohiro Ishii ◽  
Shigetomo Fukuhara
Keyword(s):  
Cell Biology ◽  
Vascular Wall ◽  
Cell Development ◽  
Platelet Derived Growth Factor ◽  
Phenotypic Analysis ◽  
Spatiotemporal Resolution ◽  
Mural Cell ◽  
Mural Cells ◽  
Recent Advances ◽  
Growth Factor Beta

Recruitment of mural cells to the vascular wall is essential for forming the vasculature as well as maintaining proper vascular functions. In recent years, zebrafish genetic tools for mural cell biology have improved substantially. Fluorescently labeled zebrafish mural cell reporter lines enable us to study, with higher spatiotemporal resolution than ever, the processes of mural cell development from their progenitors. Furthermore, recent phenotypic analysis of platelet-derived growth factor beta mutant zebrafish revealed well-conserved organotypic mural cell development and functions in vertebrates with the unique features of zebrafish. However, comprehensive reviews of zebrafish mural cells are lacking. Therefore, herein, we highlight recent advances in zebrafish mural cell tools. We also summarize the fundamental features of zebrafish mural cell development, especially at early stages, and functions.

scholarly journals Conserved and context-dependent roles for Pdgfrb signaling during zebrafish vascular mural cell development

2021 ◽  
Author(s):  
Koji Ando ◽  
Yu-Huan Shih ◽  
Lwaki Ebarasi ◽  
Ann Grosse ◽  
Daneal Portman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Coronary Vessels ◽  
Structural Defects ◽  
Mural Cell ◽  
Larval Stages ◽  
Mural Cells ◽  
Brain Pericytes ◽  
Juvenile Stages ◽  
Mutant Lines

Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.

scholarly journals FEATURES OF APONEUROSIS PATHOMORPHOLOGICAL CHANGES IN PATIENTS WITH EVENTRATION

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
Ya.Yu Voitiv ◽  
O.O. Dyadyk
Keyword(s):  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Connective Tissue ◽  
Vascular Wall ◽  
Collagen Iv ◽  
Treatment Results ◽  
Positive Expression ◽  
Connective Tissue Dysplasia ◽  
Connective Tissue Pathology

Objective – to improve the treatment results of patients with eventration by determiningthe role of undifferentiated connective tissue dysplasia in the development of thiscomplication.Material and methods. The object of the study comprises 33 patients with eventrationwho were treated in the department of thoracoabdominal surgery of Shalimov NationalInstitute of Surgery and Transplantology during 2017-2020.Results. At complex pathomorphological research of aponeurosis fragments similarmorphological changes have been revealed in groups of patients with phenotypic signsof undifferentiated connective tissue dysplasia and eventration. Immunohistochemicalexamination of tissues with monoclonal antibodies to α-SMA revealed uneven, focalexpression in smooth muscle differentiation cells and fibroblasts in both groups. In thestudies with monoclonal antibodies to Collagen IV, moderate positive expression in thebasement membrane of the blood vessels, in smooth muscle cells of the muscular layerof the vascular wall, in areas of the connective tissue was observed, that is a sign ofpathological remodeling of the connective tissue.Conclusions. Similar pathomorphological changes of the aponeurosis in groups withphenotypic signs of undifferentiated connective tissue dysplasia and post-operativeeventration confirm the role of the connective tissue pathology in the development of thiscomplication.

scholarly journals Angiocrine FSTL1 insufficiency leads to atrial and vein wall fibrosis via SMAD3 activation

2019 ◽  
Author(s):  
Haijuan Jiang ◽  
Luqing Zhang ◽  
Xuelian Liu ◽  
Wei Sun ◽  
Katsuhiro Kato ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Heart Valves ◽  
Smooth Muscle Actin ◽  
Vascular Wall ◽  
Cell Interaction ◽  
Alpha Smooth Muscle Actin ◽  
Vein Wall ◽  
Mural Cell ◽  
Smad3 Phosphorylation ◽  
Cardiovascular Fibrosis

AbstractAngiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. Here we show that loss of follistatin-like protein 1 (FSTL1) in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with Fstl1 deletion in smooth muscle cells or hematopoietic cells. We further showed that there was excessive alpha-smooth muscle actin (αSMA) associated with atrial endocardia, heart valves, veins and microvessels after the endothelial FSTL1 deletion. Consistently, there was an increase of collagen deposition as demonstrated in livers of Fstl1ECKO mutants. The SMAD3 phosphorylation was significantly enhanced and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFβ signaling in vascular mural cells of Fstl1ECKO mice. The findings imply that endothelial FSTL1 is critical for the homeostasis of atria and veins and its insufficiency may favor cardiovascular fibrosis leading to heart failure.

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