Collagen synthesis by vascular smooth muscle cells in the presence of antiproliferative polysaccharides

Abstract

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.

Structurally different RGTAs modulate collagen‐type expression by cultured aortic smooth muscle cells via different pathways involving fibroblast growth factor‐2 or transforming growth factor‐β1

“…Collagen III accumulation could be considered as a biological marker for the extent of fibrotic disorders in several tissues (46). As an extension of the in vitro antifibrotic activity of RGTA, we can establish a parallelism between the RGTA-induced decrease of collagen III production by cultured cells (8)(9)(10)28) and our recent demonstration of the direct diminution of collagen III synthesis in human intestinal tissue from Crohn's disease patients ex vivo exposed to RGTAs (47). Concerning the mechanism of the growth factor-RGTA interactions implicated in all these processes, we propose that RGTAs may act as a survival and protective agent through the maintenance and protection of the bioavaibility of preexisting and newly synthesized HBGF among those FGF-2 and TGF-β1.…”

Regulation of the collagen phenotype expression of gamma‐irradiated vascular smooth muscle cells by heparan mimetics (RGTA)

“…RGTA promote repair and remodeling of several tissues in vivo ,19–21 and act in vitro by inhibiting VSMC proliferation and decreasing total fibrillar collagen production. Furthermore, RGTA mimic heparin properties on VSMC but are devoid of heparin‐associated anticoagulant properties 13, 22, 23…”

“…They mimicked the stabilizing and protecting properties of heparan sulfates toward members of the FGF and TGF‐β1 families17, 18 and enhance their bioavaibility. RGTA promote tissue remodeling and healing in several experimental models19–21 and are devoid of anticoagulant properties 22, 23…”

Antiproliferative polysaccharides modulate distribution and phenotypic expression of collagens by gingival fibroblasts

“…Cells were used at overconfluency for all biosynthetic experiments to avoid or minimize the inhibitory effect of the investigated polysaccharides on cell proliferation. As previously described, 17,18 cells were incubated for 24 h in serumfree culture medium containing [ 3 H]proline (30 Ci/mL) and ascorbic acid (50 g/mL), without (control) or with polysaccharides (400 g/mL/10 6 cells). Under these conditions.…”

“…[14][15][16] Independently of cell proliferation regulation, we have shown that CMDBS could significantly modulate the expression of collagen biosynthesis in vascular cells. 17,18 General laws seem to sustain wound healing or tissue repair, whatever the nature and location of the injured tissue. Thus, it was interesting to investigate the potential activity of a dextran derivative on gingival fibroblasts.…”