TGF-beta and TNF-a affect cell surface proteoglycan and sialic acid expression on vascular endothelial cells.
Atherosclerosis is the formation of plaques in the arterial wall brought about by numerous events including the accumulation of oxidized low density lipoprotein (LDL), stimulation of inflammatory responses, the release of cytokines, and the attachment of monocytes to the arterial wall. Proteoglycans are implicated in many aspects of atherosclerosis including the metabolism of lipoproteins, regulation of cytokine activity, cell adhesion, and modification of the extracellular matrix. Due to their complex role in molecular recognition and cellular adhesion, the glycosaminoglycan (GAG) chains attached to the proteoglycan core and sialic acids on the terminal ends of the glycan chains are of interest. This study investigated the effects of exposure to transforming growth factor-beta 1 (TGF-beta 1) and tumor necrosis factor-a (TNF-a) on the expression of cell surface GAGs and sialic acids on human umbilical vein endothelial cells (HUVECs). Initial results show that TGF-beta 1 affected GAG expression compared to a control condition. Results also show that the combination of TGF-beta 1 and TNF-a affected GAG expression differently than does TGF-beta 1 alone. Additionally, TNF-a decreased the number of sialic acid residues per cell and TGF-beta 1 slightly upregulated sialic acid expression as compared to the control. The combination of the two cytokines showed a larger upward trend in this value. These data indicate that TNF-a and TGF-beta 1 play a role in the expression of GAG chains and sialic acids on the cell surface. Further study may clarify the implications of these findings for atherosclerosis.
Doiron
Amber L
AL
Department of Chemical Engineering, Colorado State University, Fort Collins, CO 80523-1370, USA.
Kirkpatrick
Allison P
AP
Rinker
Kristina D
KD
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D006025:Glycosaminoglycans; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019158:N-Acetylneuraminic Acid