Atheromatosis of arterial intima

2016 ◽  
Vol 94 (8) ◽  
pp. 582-590
Author(s):  
Vladimir N. Titov ◽  
T. A. Rozhkova ◽  
V. A. Amelyushkina
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Proteolytic Enzymes ◽  
Muscle Cells ◽  
Acid Hydrolases ◽  
The Matrix ◽  
Arterial Intima ◽  
Hydrolysis Of

Phylogenetically late arterial intima of the elastic type contains no proteins for the transfer of ligandless oxidized low density lipoproteins (LDLP) for sedentary macrophages adsorbed on the matrix. Phylogenetically early cells realize the extracellular digestive reaction by releasing proteolytic enzymes (metalloproteinases) into intimal matrix that hydrolize matrix proteoglycans, adsorbed ligandless LDLP, detritus, and complete lysosomal hydrolysis of the most hydrophobic polyenic cholesterol esters (poly-ECS). Smooth muscle cells migrate from the middle muscular layer of the arterial wall, change their contractile phenotype to secretory one, and synthesize in situ de novomatrix proteoglycans. The arterial wall has three layers (monolayer endothelium, intimal media (smooth muscle cells), and adventitia) only in elastic type arteries. It is desirable to elucidate functional differences between phylogenetically early sedentarymacrophages and monocytes-macrophages of later origin and understand whether theydepends on specific features of activity of scavenger eceptors, CD36 translocases, expression of acid hydrolases synthesis for poly-ECS or realization of the extracellular digestion reaction. We believe that formation of atheromatous masses takes place in the matrix of arterial intima rather than in lysosomes taking into account limited possibilities for monocytes-macrophages to realize endocytosis of ligandless LDLP from the matrix. Given that atheromatosis is a syndrome of deficit of essential polyenic fatty acids (PFA) in the cells, intimal atheromatosisshould be regarded only as partial utilization of excess PFA in the matrix of elastic type arteries. At later stages of phylogenesis, intima was formed from media smooth muscle cells.

scholarly journals Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages.

1980 ◽  
Vol 152 (5) ◽  
pp. 1340-1357 ◽  
Author(s):  
Z Werb ◽  
M J Banda ◽  
P A Jones
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Connective Tissue ◽  
Smooth Muscle Cells ◽  
Conditioned Medium ◽  
Proteolytic Enzymes ◽  
Muscle Cells ◽  
Granulocyte Elastase ◽  
Elastin Degradation ◽  
The Matrix

We have investigated the ability of neutral and lysosomal enzymes of mouse macrophages to degrade the insoluble extracellular matrices secreted by smooth muscle cells, endothelial cells, and fibroblasts. Matrices produced by smooth muscle cells contained glycoproteins, elastin, and collagens, but matrices of endothelial cells and fibroblasts contained no elastin. Sequential enzyme digestion of residual matrix revealed that plasmin, a product of macrophage plasminogen activation, degraded 50-70% of the glycoprotein in the matrices but did not degrade the elastin or the collagens. Purified macrophage elastase degraded glycoprotein and elastin components but had no effect on the collagens. The rate of elastin degradation by macrophage elastase was decreased in the presence of the glycoproteins. In contrast, human granulocyte elastase effectively degraded the matrix glycoproteins, elastin, and, to a lesser extent, collagens, Mammalian collagenase degraded only collagens. Conditioned medium from resident and inflammatory macrophages, containing mixtures of the secreted proteinases, degraded the glycoprotein and elastin components of the matrices. However, conditioned medium was less effective in degrading matrix than comparable amounts of purified macrophage elastase because > 90% of the elastase in the medium was in a latent form. Inclusion of plasminogen in the assays accelerated degradation. In the presence of plasminogen, glycoproteins were degraded readily by medium from P388D1, pyran copolymer-, thioglycollate-, and periodate-elicited macrophages and, to a lesser extent, by medium from endotoxin-elicited and resident macrophages; medium from P388D1, thioglycollate-, and periodate-elicited macrophages was most effective in elastin degradation, and resident, endotoxin-elicited and pyran copolymer-elicited macrophages degraded almost no elastin. The macrophage cathepsins D and B degraded all the matrix components at an optimum pH of 5.5 and acted with the secreted neutral proteinases to degrade the connective tissue macromolecules to amino acids and oligopeptides. These data indicate that macrophages at inflammatory sites contain and secrete proteolytic enzymes that could degrade the 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.

Distribution of shear stress over smooth muscle cells in deformable arterial wall

2008 ◽  
Vol 46 (7) ◽  
pp. 649-657 ◽  
Author(s):  
Mahsa Dabagh ◽  
Payman Jalali ◽  
Yrjö T. Konttinen ◽  
Pertti Sarkomaa
Keyword(s):  
Shear Stress ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Muscle Cells

Computational study on phase lag of arterial-wall motion for assessment of plaque vulnerability

2020 ◽  
Vol 234 (5) ◽  
pp. 517-526
Author(s):  
Pengsrorn Chhai ◽  
Kyehan Rhee
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Wall Motion ◽  
Arterial Wall ◽  
Computational Study ◽  
Muscle Cells ◽  
Phase Lag ◽  
Plaque Vulnerability ◽  
Wall Displacement ◽  
Lipid Core

The wall motion of atherosclerotic plaque was analyzed using a computational method, and the effects of tissue viscoelasticity, fibrosis thickness, and lipid-core stiffness on wall displacement waveforms were examined. The viscoelasticity of plaque tissues was modeled using a time Prony series with four Maxwell elements. Computational simulation of tissue indentation tests showed the validity of the proposed viscoelastic constitutive models. Decreasing the relative moduli of the viscoelastic model reduced their viscous characteristics while enhancing the stiffness of the wall, which corresponded with the effects of decreased smooth muscle cells content. A finite-element analysis was conducted for atherosclerotic wall models and wall displacement waveforms were computed. The phase difference between the first harmonics of pressure and displacement waves was selected to represent the time delay of the wall motion. As the relative modulus decreased, the wall displacement and phase lag decreased. A thinner wall and softer lipid core corresponded to a greater wall displacement and smaller phase lag. Because the phase lag of the arterial-wall motion was smaller for the plaque with a thinner cap, lower smooth muscle cells content, and softer lipid core (all features of plaques with high rupture risk), first harmonics of pressure and displacement waves can be used as an index to assess plaque vulnerability.

scholarly journals Angiotensin II-induced phosphatidylcholine hydrolysis in cultured vascular smooth-muscle cells. Regulation and localization

1991 ◽  
Vol 276 (1) ◽  
pp. 19-25 ◽  
Author(s):  
B Lassègue ◽  
R W Alexander ◽  
M Clark ◽  
K K Griendling
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Kinase C ◽  
Hydrolysis Of

In cultured vascular smooth-muscle cells (VSMC), angiotensin II (AngII) induces a biphasic, sustained increase in diacylglycerol (DG) of unclear origin. To determine whether hydrolysis of phosphatidylcholine (PC) is a possible source of DG, we labelled cellular PC with [3H]choline, and measured the formation of intra- and extra-cellular [3H]choline and [3H]phosphocholine after stimulation with AngII. AngII induced a concentration-dependent release of choline from VSMC that was significant at 2 min and was sustained over 20 min. In contrast, accumulation of choline inside the cells was very slight. AngII also increased the formation of [3H]myristate-labelled phosphatidic acid, and, in the presence of ethanol, of [3H]phosphatidylethanol, characteristic of a phospholipase D (PLD) activity. Extracellular release of choline was partially inhibited by removal of extracellular Ca2+ (54 +/- 9% inhibition at 10 min) or inhibition of receptor processing by phenylarsine oxide (79 +/- 8% inhibition at 20 min). The protein kinase C activator phorbol myristate acetate also stimulated a large release of choline after a 5 min lag, which was unaffected by the Ca2+ ionophore ionomycin, but was additive with AngII stimulation. Down-regulation of protein kinase C by a 24 h incubation with phorbol dibutyrate (200 nM) decreased basal choline release, but had no effect on AngII stimulation. We conclude that AngII induces a major PC hydrolysis, probably mainly via PLD activation. This reaction is partially dependent on Ca2+ and is independent of protein kinase C, and appears to be mediated by cellular processing of the receptor-agonist complex. Our results are consistent with a preferential hydrolysis of PC from the external leaflet of the plasmalemma, and raise the possibility that PC hydrolysis occurs in specialized ‘signalling domains’ in VSMC.

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