Monocyte prostaglandins inhibit procollagen secretion by human vascular smooth muscle cells: implications for plaque stability

Extracellular matrix remodelling occurs during atherosclerosis dictating th e structure of the plaque and thus the resistance to rupture. Monocytes and macrophages are believed to play a role in this remodelling. In the presen t study, filter-separated co-culture has been used to study the effect of m onocytes on procollagen turnover by human vascular smooth muscle cells (VSM C). In this system, freshly isolated human peripheral blood monocytes inhib ited procollagen secretion from VSMC without affecting either degradation o f 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 cyclooxygen ase-dependent. Pre-incubation of each cell type with indomethacin demonstra ted that monocyte, but not VSMC cyclooxygenase was required. Thus, the inhi bitory effect on procollagen secretion was due, most likely, to monocyte pr ostaglandins. Neither inhibition of thromboxane synthetase, nor blocking IL -1 activity, reduced the inhibitory activity. Addition of prostaglandins PG E(1), PGE(2) and PGF(2 alpha) to VSMC cultures caused a reduction in procol lagen secretion which was equivalent to, but was not additive with, the max imal effect achieved by monocytes. Monocytes and macrophages are a major so urce of prostaglandins and these molecules are likely to play an important role in collagen turnover within lesions. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.