Collagen synthesis by vascular smooth muscle cells in the presence of antiproliferative polysaccharides.
Production of various components of the extracellular matrix (ECM) modulates biological functions of the vascular tissue. This process is generally amplified in pathologic states as atherosclerosis. Atheroma originates from smooth muscle cells (SMC) which have migrated and proliferated in the vascular intima. In this study we investigated protein synthesis, collagen synthesis, and types I, III, and V collagen distribution by SMC in the presence of three families of watersoluble polysaccharides, heparin, fucans, and derivatized dextrans. We observed that fucan and derivatized dextran were able, as was heparin, to inhibit rat aortic SMC growth in culture. We then analyzed collagen modulation by measuring the incorporation of the radiolabeled precursor (3H)-proline into vascular SMC. Our results showed uncoupling of the antiproliferative capacity with collagen biosynthesis. However, fucan, the most antiproliferative polysaccharide, was also the most active in inhibiting protein and collagen synthesis. In addition, compounds that decreased total collagen synthesis preferentially increased the proportion of cell-associated collagen. Interestingly, only the antiproliferative polysaccharides inhibited significantly type V collagen biosynthesis. These new biomaterials appear to be valuable tools to study and control extracellular-matrix interactions with cells from the vascular walls.
Logeart
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LRM, CNRS URA 502, Université Paris XIII, Villetaneuse, France.
Letourneur
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Jozefonvicz
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J
Kern
P
P
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D003911:Dextrans / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats
D000925:Anticoagulants; D003911:Dextrans; D011134:Polysaccharides; D006493:Heparin; D003094:Collagen