Elastogenic effects of exogenous hyaluronan oligosaccharides on vascular smooth muscle cells.
Identifieur interne : 002D30 ( Main/Exploration ); précédent : 002D29; suivant : 002D31Elastogenic effects of exogenous hyaluronan oligosaccharides on vascular smooth muscle cells.
Auteurs : Binata Joddar [États-Unis] ; Anand RamamurthiSource :
- Biomaterials [ 0142-9612 ] ; 2006.
Descripteurs français
- KwdFr :
- Acide hyaluronique (), Acide hyaluronique (métabolisme), Acide hyaluronique (pharmacologie), Animaux, Aorte (cytologie), Cellules cultivées, Collagène (métabolisme), Collagène (ultrastructure), Fibrillines, Matrice extracellulaire (), Matrice extracellulaire (métabolisme), Muscles lisses vasculaires (cytologie), Myocytes du muscle lisse (), Myocytes du muscle lisse (cytologie), Myocytes du muscle lisse (métabolisme), Oligosaccharides (), Oligosaccharides (métabolisme), Oligosaccharides (pharmacologie), Prolifération cellulaire, Protéines des microfilaments (métabolisme), Rats, Régénération tissulaire guidée (), Élastine (métabolisme), Élastine (ultrastructure).
- MESH :
- cytologie : Aorte, Muscles lisses vasculaires, Myocytes du muscle lisse.
- métabolisme : Acide hyaluronique, Collagène, Matrice extracellulaire, Myocytes du muscle lisse, Oligosaccharides, Protéines des microfilaments, Élastine.
- pharmacologie : Acide hyaluronique, Oligosaccharides.
- Acide hyaluronique, Animaux, Cellules cultivées, Collagène, Fibrillines, Matrice extracellulaire, Myocytes du muscle lisse, Oligosaccharides, Prolifération cellulaire, Rats, Régénération tissulaire guidée, Élastine.
English descriptors
- KwdEn :
- Animals, Aorta (cytology), Cell Proliferation, Cells, Cultured, Collagen (metabolism), Collagen (ultrastructure), Elastin (metabolism), Elastin (ultrastructure), Extracellular Matrix (chemistry), Extracellular Matrix (metabolism), Fibrillins, Guided Tissue Regeneration (methods), Hyaluronic Acid (chemistry), Hyaluronic Acid (metabolism), Hyaluronic Acid (pharmacology), Microfilament Proteins (metabolism), Muscle, Smooth, Vascular (cytology), Myocytes, Smooth Muscle (cytology), Myocytes, Smooth Muscle (drug effects), Myocytes, Smooth Muscle (metabolism), Oligosaccharides (chemistry), Oligosaccharides (metabolism), Oligosaccharides (pharmacology), Rats.
- MESH :
- chemical , chemistry : Hyaluronic Acid, Oligosaccharides.
- chemical , metabolism : Collagen, Elastin, Hyaluronic Acid, Microfilament Proteins, Oligosaccharides.
- chemistry : Extracellular Matrix.
- cytology : Aorta, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle.
- drug effects : Myocytes, Smooth Muscle.
- metabolism : Extracellular Matrix, Myocytes, Smooth Muscle.
- methods : Guided Tissue Regeneration.
- chemical , pharmacology : Hyaluronic Acid, Oligosaccharides.
- chemical , ultrastructure : Collagen, Elastin.
- Animals, Cell Proliferation, Cells, Cultured, Fibrillins, Rats.
Abstract
Prior studies suggest that hyaluronan (HA), a glycosaminoglycan, may upregulate innately poor elastin matrix synthesis by adult vascular smooth muscle cells (SMCs). HA scaffolds could thus be useful to regenerate damaged vascular elastin. In an earlier study, we established that the elastogenic effects of non-oligomeric HA are fragment size- and/or dose-specific. We currently investigate the pro-elastogenic effects of exogenous HA oligomers on rat aortic smooth muscle cells (RASMCs). RASMCs were cultured with pure HA oligomers (4-mers) and mixtures (4-8mers) obtained by enzymatic digestion of long-chain HA (MW approximately 2000kDa). Polyacrylamide gel electrophoresis (PAGE)/Matrix Assisted Laser Desorption/Ionization Spectroscopy Time-Of-Flight Analysis (MALDI-TOF) showed HA digestates to contain a mixture of 4-8mers with a predominance of 4-mers (75+/-0.4% w/w). Cell layers supplemented with both pure HA 4-mers or oligomer mixtures showed proliferation levels similar to non-HA controls over 21 days of culture. Pure 4-mers and oligomer mixtures enhanced DNA-normalized output of tropoelastin by 1.6 and 1.8 times, respectively, and that of matrix elastin by approximately 2.7 times relative to controls. Sodium dodecyl sulfate (SDS)-PAGE/Western Blot and a desmosine assay semi-quantitatively confirmed the observed biochemical trends for tropoelastin and matrix elastin, respectively. HA oligomers induced enhanced synthesis of the elastin crosslinker, desmosine, and appeared to stabilize the elastin matrix by suppression of elastin-laminin receptor (ELR) activity relative to controls. Transmission electron micrographs (TEMs) showed elastin deposits within oligomer-supplemented cultures to be distinct, longitudinally oriented, aggregating fibrils, and clumps, and to be less abundant and mostly amorphous in controls. HA oligomers preserved normal fibrillin-mediated elastin matrix deposition. Results suggest that HA oligos are highly pro-elastogenic, promote elastin fibril formation, and stabilize elastin matrix and may thus be usefully incorporated into scaffolds for guided elastin regeneration.
DOI: 10.1016/j.biomaterials.2006.07.020
PubMed: 16899292
Affiliations:
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Le document en format XML
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<term>Aorta (cytology)</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Collagen (metabolism)</term>
<term>Collagen (ultrastructure)</term>
<term>Elastin (metabolism)</term>
<term>Elastin (ultrastructure)</term>
<term>Extracellular Matrix (chemistry)</term>
<term>Extracellular Matrix (metabolism)</term>
<term>Fibrillins</term>
<term>Guided Tissue Regeneration (methods)</term>
<term>Hyaluronic Acid (chemistry)</term>
<term>Hyaluronic Acid (metabolism)</term>
<term>Hyaluronic Acid (pharmacology)</term>
<term>Microfilament Proteins (metabolism)</term>
<term>Muscle, Smooth, Vascular (cytology)</term>
<term>Myocytes, Smooth Muscle (cytology)</term>
<term>Myocytes, Smooth Muscle (drug effects)</term>
<term>Myocytes, Smooth Muscle (metabolism)</term>
<term>Oligosaccharides (chemistry)</term>
<term>Oligosaccharides (metabolism)</term>
<term>Oligosaccharides (pharmacology)</term>
<term>Rats</term>
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<term>Acide hyaluronique (métabolisme)</term>
<term>Acide hyaluronique (pharmacologie)</term>
<term>Animaux</term>
<term>Aorte (cytologie)</term>
<term>Cellules cultivées</term>
<term>Collagène (métabolisme)</term>
<term>Collagène (ultrastructure)</term>
<term>Fibrillines</term>
<term>Matrice extracellulaire ()</term>
<term>Matrice extracellulaire (métabolisme)</term>
<term>Muscles lisses vasculaires (cytologie)</term>
<term>Myocytes du muscle lisse ()</term>
<term>Myocytes du muscle lisse (cytologie)</term>
<term>Myocytes du muscle lisse (métabolisme)</term>
<term>Oligosaccharides ()</term>
<term>Oligosaccharides (métabolisme)</term>
<term>Oligosaccharides (pharmacologie)</term>
<term>Prolifération cellulaire</term>
<term>Protéines des microfilaments (métabolisme)</term>
<term>Rats</term>
<term>Régénération tissulaire guidée ()</term>
<term>Élastine (métabolisme)</term>
<term>Élastine (ultrastructure)</term>
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<term>Oligosaccharides</term>
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<term>Elastin</term>
<term>Hyaluronic Acid</term>
<term>Microfilament Proteins</term>
<term>Oligosaccharides</term>
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<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Extracellular Matrix</term>
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<term>Muscles lisses vasculaires</term>
<term>Myocytes du muscle lisse</term>
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<term>Myocytes, Smooth Muscle</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Extracellular Matrix</term>
<term>Myocytes, Smooth Muscle</term>
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<term>Collagène</term>
<term>Matrice extracellulaire</term>
<term>Myocytes du muscle lisse</term>
<term>Oligosaccharides</term>
<term>Protéines des microfilaments</term>
<term>Élastine</term>
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<term>Oligosaccharides</term>
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<term>Oligosaccharides</term>
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<term>Matrice extracellulaire</term>
<term>Myocytes du muscle lisse</term>
<term>Oligosaccharides</term>
<term>Prolifération cellulaire</term>
<term>Rats</term>
<term>Régénération tissulaire guidée</term>
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<front><div type="abstract" xml:lang="en">Prior studies suggest that hyaluronan (HA), a glycosaminoglycan, may upregulate innately poor elastin matrix synthesis by adult vascular smooth muscle cells (SMCs). HA scaffolds could thus be useful to regenerate damaged vascular elastin. In an earlier study, we established that the elastogenic effects of non-oligomeric HA are fragment size- and/or dose-specific. We currently investigate the pro-elastogenic effects of exogenous HA oligomers on rat aortic smooth muscle cells (RASMCs). RASMCs were cultured with pure HA oligomers (4-mers) and mixtures (4-8mers) obtained by enzymatic digestion of long-chain HA (MW approximately 2000kDa). Polyacrylamide gel electrophoresis (PAGE)/Matrix Assisted Laser Desorption/Ionization Spectroscopy Time-Of-Flight Analysis (MALDI-TOF) showed HA digestates to contain a mixture of 4-8mers with a predominance of 4-mers (75+/-0.4% w/w). Cell layers supplemented with both pure HA 4-mers or oligomer mixtures showed proliferation levels similar to non-HA controls over 21 days of culture. Pure 4-mers and oligomer mixtures enhanced DNA-normalized output of tropoelastin by 1.6 and 1.8 times, respectively, and that of matrix elastin by approximately 2.7 times relative to controls. Sodium dodecyl sulfate (SDS)-PAGE/Western Blot and a desmosine assay semi-quantitatively confirmed the observed biochemical trends for tropoelastin and matrix elastin, respectively. HA oligomers induced enhanced synthesis of the elastin crosslinker, desmosine, and appeared to stabilize the elastin matrix by suppression of elastin-laminin receptor (ELR) activity relative to controls. Transmission electron micrographs (TEMs) showed elastin deposits within oligomer-supplemented cultures to be distinct, longitudinally oriented, aggregating fibrils, and clumps, and to be less abundant and mostly amorphous in controls. HA oligomers preserved normal fibrillin-mediated elastin matrix deposition. Results suggest that HA oligos are highly pro-elastogenic, promote elastin fibril formation, and stabilize elastin matrix and may thus be usefully incorporated into scaffolds for guided elastin regeneration.</div>
</front>
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