scholarly journals Mechanical contribution of vascular smooth muscle cells in the tunica media of artery

2019 ◽  
Vol 8 (1) ◽  
pp. 50-60
Author(s):  
Hozhabr Mozafari ◽  
Changchun Zhou ◽  
Linxia Gu
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Arterial Wall ◽  
Muscle Cells ◽  
Computational Studies ◽  
Ecm Proteins

Abstract The stiffness of arterial wall in response to cardiovascular diseases has been associated with the changes in extracellular matrix (ECM) proteins, i.e., collagen and elastin. Vascular smooth muscle cells (VSMCs) helped to regulate the ECM reorganizations and thus contributed to arterial stiffness. This article reviewed experimental and computational studies for quantifying the roles of ECM proteins and VSMCs in mechanical properties of arteries, including nanostructure and mechanical properties of VSMCs and ECMs, cell-ECM interaction, and biomimetic gels/scaffolds induced contractile properties and phenotype changing of VSMCs. This work will facilitate our understanding of how the microenvironments and mechanotransduction impact and regulate the arterial adaptation.

scholarly journals MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells

2005 ◽  
Vol 202 (5) ◽  
pp. 663-671 ◽  
Author(s):  
Sergey Filippov ◽  
Gerald C. Koenig ◽  
Tae-Hwa Chun ◽  
Kevin B. Hotary ◽  
Ichiro Ota ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Arterial Wall ◽  
Neointimal Hyperplasia ◽  
Muscle Cells

During pathologic vessel remodeling, vascular smooth muscle cells (VSMCs) embedded within the collagen-rich matrix of the artery wall mobilize uncharacterized proteolytic systems to infiltrate the subendothelial space and generate neointimal lesions. Although the VSMC-derived serine proteinases, plasminogen activator and plasminogen, the cysteine proteinases, cathepsins L, S, and K, and the matrix metalloproteinases MMP-2 and MMP-9 have each been linked to pathologic matrix-remodeling states in vitro and in vivo, the role that these or other proteinases play in allowing VSMCs to negotiate the three-dimensional (3-D) cross-linked extracellular matrix of the arterial wall remains undefined. Herein, we demonstrate that VSMCs proteolytically remodel and invade collagenous barriers independently of plasmin, cathepsins L, S, or K, MMP-2, or MMP-9. Instead, we identify the membrane-anchored matrix metalloproteinase, MT1-MMP, as the key pericellular collagenolysin that controls the ability of VSMCs to degrade and infiltrate 3-D barriers of interstitial collagen, including the arterial wall. Furthermore, genetic deletion of the proteinase affords mice with a protected status against neointimal hyperplasia and lumen narrowing in vivo. These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix.

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.

Abstract 496: Extracellular Matrix Secretion by Vascular Smooth Muscle Cells: Role of MiR-195 and MiR-29b

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anna Zampetaki ◽  
Xiaoke Yin ◽  
Ursula Mayr ◽  
Renata Gomes ◽  
Sarah Langley ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Vascular Smcs

Rationale: Extracellular matrix (ECM) remodeling is a key function of vascular smooth muscle cells (SMCs). MicroRNAs (miRNAs), in particular the miR-29 family and miR-195, have been implicated in the control of ECM secretion. Objective: To perform a proteomics comparison of miRNA effects on ECM production by vascular SMCs. Methods and Results: Murine SMCs were transfected with miRNA mimics and antimiRs of miR-29b and miR-195, and their conditioned medium was analyzed by mass spectrometry. Both miRNAs targeted a cadre of ECM proteins, including proteoglycans, collagens, proteases, elastin and proteins associated with elastic microfibrils, albeit miR-29 showed a stronger effect. The proteomics findings were subsequently validated at the transcription level using quantitative polymerase chain reaction. Similar to miR-29, in vivo inhibition of miR-195 by intraperitoneal injection of cholesterol bound antagomiRs led to significant alterations of elastin expression in murine aortas. Since elastin degradation is a key event in aortic aneurysm formation, we investigated miR-195 expression in patients. In human aortic aneurysmal tissue, miR-195 expression was reduced compared to non-aneurysmal tissue. In plasma, a comparison between male patients with abdominal aortic aneurysms and controls matched for diabetes and hypertension returned a panel of five highly correlated miRNAs: miR-195, miR-125b, miR-148a, miR-20a and miR-340 showed significant inverse associations with the presence of abdominal aortic aneurysms and aortic diameter, with miR-195 dominating in terms of association strength. Conclusions: Using proteomic analysis, we compared the effect of miR-29 and miR-195 on ECM secretion by vascular SMCs and identified novel miRNA targets. Findings in patients support an important role for miR-195 in vascular remodeling as evidenced by reduced miR-195 expression in human aneurysmal tissue and an inverse correlation between plasma miR-195 levels and aortic diameter.

The Effects of Extracellular Matrix Protein Insufficiency and Treatment on the Stiffness of Arterial Smooth Muscle Cells

2013 ◽  
Author(s):  
Gabriela Espinosa ◽  
Lisa Bennett ◽  
William Gardner ◽  
Jessica Wagenseil
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Elastic Tissue ◽  
Newborn Mice ◽  
Ecm Proteins ◽  
Wall Stiffness ◽  
Deficient Mice

Increased arterial stiffness is directly correlated with hypertension and cardiovascular disease. Stiffness of the conducting arteries is largely determined by the extracellular matrix (ECM) proteins in the wall, such as collagen and elastin, produced by the smooth muscle cells (SMCs) found in the medial layer. Elastin is deposited as soluble tropoelastin and is later crosslinked into elastin fibers. Newborn mice lacking the elastin protein ( Eln−/−) have increased arterial wall stiffness and SMCs with altered proliferation, migration and morphology [1]. Vessel elasticity is also mediated by other ECM proteins, such as fibulin-4. Elastic tissue, such as lung, skin, and arteries, from fibulin-4 deficient ( Fbln4−/−) mice show no decrease in elastin content, but have reduced elasticity due to disrupted elastin fibers [2]. Arteries from both elastin and fibulin-4 deficient mice have been previously studied, but the mechanical properties of their SMCs have not been investigated. Recent experiments comparing arterial SMCs from old and young animals suggest that mechanical properties of the SMCs themselves may contribute to changes in wall stiffness [3]. Hence, we investigated the stiffness of isolated arterial SMCs from elastin and fibulin-4 deficient mice using atomic force microscopy (AFM). In addition, we studied the effects of two elastin treatments on the mechanical properties of SMCs from Eln+/+ and Eln−/− mice. Differences between the treatments may elucidate the importance of soluble versus crosslinked elastin on single cell stiffness.

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