THU0551 Secretory Phospholipases as Mediators of Inflammatory and Proatheromatous Changes in Rheumatic Diseases
Authors: W. Pruzanski, A. Kuksis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Inflammatory vascular changes and enhanced atheromatosis are well known in rheumatic diseases. Mitogenesis of vascular smooth muscle cells (VSMC) in above conditions is of prime importance. Secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>), which is known to induce mitogenesis, was found in and cloned from the synovial fluid (1,2). High serum levels of sPLA<sub>2</sub> were found in various rheumatic diseases (3-6). sPLA<sub>2</sub> was found in synovial cells (7) human cartilage (8) and chondrocytes (9). Pro-inflammatory effect of sPLA<sub>2</sub> on joint tissue was reported (10). <h3>Objectives</h3> To investigate the role of sPLA<sub>2</sub> IIA, V and X on mitogenesis of VSMC, release of PGE<sub>2</sub> and LTB<sub>4</sub> and effect on lipoproteins. Furthermore, the effects of enzyme hydrolysis of pro-inflammatory products of Oxo-PtdCho were investigated. <h3>Methods</h3> Cultures of VSMC, study of mitogenesis, origins of sPLA<sub>2</sub>9s and lipoproteins were reported (11). The analyses of the products of PtdCho oxidation, such as core aldehydes, isoprostanes, hydroxides and hydroxyperoxides were done by LC/ESI-MS.PGE<sub>2</sub> and LTB<sub>4</sub> release were tested by EIA systems. <h3>Results</h3> Exposure of VSMC to sPLA<sub>2</sub> IIA or X did not increase mitogenesis, whereas exposure to grV markedly increased it in a dose/time fashion. Likewise, VSMC exposed to HDL or LDL hydrolysed by sPLA<sub>2</sub> V (and less by X) became mitogenic. Interaction of sPLA<sub>2</sub> with lipoproteins showed that hydrolysis of HDL and LDL by sPLA<sub>2</sub>9s and the impact on mitogenesis were invariably enhanced in order V&gt;X&gt;IIA. Release of PGE<sub>2</sub> was enhanced by sPLA<sub>2</sub> X and LTB<sub>4</sub> by gr X and V. Investigation of the products of lipoproteins hydrolysis showed that there is formation of core aldehydes, isoprostanes, hydroxides and hydroperoxides of PtdCho. sPLA<sub>2</sub> grV hydrolysed hydroxides and hydroxyperoxides of linoleolyl GroPCho in preference to arachidonoyl GroPCho while groups IIA and X did the opposite. <h3>Conclusions</h3> The above studies show diverse activity of sPLA<sub>2</sub>9s gr IIA, V and X on mitogenesis of VSMC (early activation of inflammation) and on release of PGE<sub>2</sub> and LTB<sub>4</sub> from VSMC (late phase of proinflammatory activity). Further study showed differences between the effects of sPLA<sub>2</sub> V as opposed to IIA and X on mitogenesis and on hydrolysis of lipoproteins, showing the complexity of mitogenic proinflammatory response. Further studies directed to block sPLA<sub>2</sub>9s especially V in inflammation and enhanced atherogenesis in rheumatic diseases is advisable. <h3>References</h3> Stefanski E. et. al. J. Biochem.100:1297, 1986. Seilhamer J.J. et al. J. Biol. Chem. 264:5335, 1981. Pruzanski W. et al. J. Rheumat. 15:1601, 1988. J. Rheumat. 18:117, 1991. J. Rheumat. 21:1951, 1994. J. Rheumat. 21:252, 1994. J. Rheumat. 15:791, 1988. J. Rheumat. 17:569, 1990. J. Rheumat. 17:1386, 1990. J. Rheumat. 13:1990, 1986. Lab. Invest. 81:757, 2001. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1520