Monocyte prostaglandins inhibit procollagen secretion by human vascular smooth muscle cells: implications for plaque stability.
Extracellular matrix remodelling occurs during atherosclerosis dictating the structure of the plaque and thus the resistance to rupture. Monocytes and macrophages are believed to play a role in this remodelling. In the present study, filter-separated co-culture has been used to study the effect of monocytes on procollagen turnover by human vascular smooth muscle cells (VSMC). In this system, freshly isolated human peripheral blood monocytes inhibited procollagen secretion from VSMC without affecting either degradation of procollagen, or DNA synthesis by the VSMC. Insertion of a 12 kDa dialysis membrane between the two cell types and treatment with indomethacin showed that the inhibitory factor was of low molecular weight and was cyclooxygenase-dependent. Pre-incubation of each cell type with indomethacin demonstrated that monocyte, but not VSMC cyclooxygenase was required. Thus, the inhibitory effect on procollagen secretion was due, most likely, to monocyte prostaglandins. Neither inhibition of thromboxane synthetase, nor blocking IL-1 activity, reduced the inhibitory activity. Addition of prostaglandins PGE1, PGE2 and PGF2alpha to VSMC cultures caused a reduction in procollagen secretion which was equivalent to, but was not additive with, the maximal effect achieved by monocytes. Monocytes and macrophages are a major source of prostaglandins and these molecules are likely to play an important role in collagen turnover within lesions.
Department of Pathology, University of Cambridge, UK. cfitzsimmons@mole.bio.cam.ac.uk
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Proudfoot
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D001158:Arteries / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D013928:Thromboxane A2 / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011347:Procollagen; D011453:Prostaglandins; D013928:Thromboxane A2; D004247:DNA; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin