Interaction of endothelial cells and fibroblasts with modified fibrin networks: role in atherosclerosis.
Fibrinogen has been recognised in recent years as an independent risk factor in athero/thrombogenesis. However, the mechanism by which elevated fibrinogen translates into higher incidence of atherosclerosis is not known. One possible mechanism may be through the modification of fibrin. While it is already known that fibrin network is altered in disease states like peripheral vascular disease, diabetes, hypercholesterolaemia and myocardial infarction, the influence of altered fibrin network structure on growth and function of endothelial cells (EC) and fibroblasts (FB) requires investigation. Fibrin network structure in plasma clots was modified by changing pH and characterised using established biophysical methods. PGI(2), von Willebrand Factor (vWF), t-PA and PAI-1 were measured to evaluate changes in cell function induced by modified fibrin structure. In general, networks composed of thin fibres induced growth over their entire layer. Networks composed of thick fibres and open matrix promoted infiltration of cells into gel matrix and growth of macrovascular structures. Furthermore, thin fibres promoted a more prothrombotic environment as observed from changes in cell biochemical function. Fibrin, whilst initially acting as a scaffolding for cellular and biochemical processes, may also alter cell function and determine the progress of atherosclerosis.
Shats
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EA
Vascular and Thrombosis Research Unit, Woden Valley Hospital, Canberra, Australia.
Nair
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CH
Dhall
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DP
D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005337:Fibrin / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008858:Microscopy, Phase-Contrast; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000096:biosynthesis
D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D005337:Fibrin; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator