TY - JOUR
T1 - Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation
AU - Bot, Martine
AU - de Jager, Saskia C. A.
AU - MacAleese, Luke
AU - Lagraauw, H. Maxime
AU - van Berkel, Theo J. C.
AU - Quax, Paul H. A.
AU - Kuiper, Johan
AU - Heeren, Ron M. A.
AU - Biessen, Erik A. L.
AU - Bot, Ilze
PY - 2013/5
Y1 - 2013/5
N2 - Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.-Bot, M., S. C. A. de Jager, L. MacAleese, H. M. Lagraauw, T. J. C. van Berkel, P. H. A. Quax, J. Kuiper, R. M. A. Heeren, E. A. L. Biessen, and I. Bot. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation. J. Lipid Res. 2013. 54: 1265-1274.
AB - Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.-Bot, M., S. C. A. de Jager, L. MacAleese, H. M. Lagraauw, T. J. C. van Berkel, P. H. A. Quax, J. Kuiper, R. M. A. Heeren, E. A. L. Biessen, and I. Bot. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation. J. Lipid Res. 2013. 54: 1265-1274.
KW - atherosclerosis
KW - plaque stability
KW - macrophage
U2 - 10.1194/jlr.M032862
DO - 10.1194/jlr.M032862
M3 - Article
SN - 0022-2275
VL - 54
SP - 1265
EP - 1274
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 5
ER -