Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

Frontiers in Physiology
Chun GuXi Chen

Abstract

Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM) degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively (r = 0.31, P < 0.05) and both elevated significantly in patients with acute myocardial infarct (AMI). Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX), LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments in vitro were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. ...Continue Reading

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Citations

Jan 11, 2020·Journal of Biomolecular Structure & Dynamics·Saima S MirZuhaib F Bhat
Jun 4, 2020·International Journal of Molecular Sciences·Wioletta OlejarzGrażyna Kubiak-Tomaszewska
Oct 22, 2020·Mediators of Inflammation·Tiewei LiJunmei Yang
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Dec 18, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric EngelbrechtTimothy Hla
Sep 1, 2019·Journal of Autoimmunity·Christiana MagkriotiVassilis Aidinis
May 1, 2021·International Journal of Molecular Sciences·Michal Kowara, Agnieszka Cudnoch-Jedrzejewska
Dec 23, 2021·Experimental and Therapeutic Medicine·Xuejun WangYu Zhuang

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Methods Mentioned

BETA
light microscopy
PCR
electrophoresis
Assay
ELISA

Software Mentioned

SPSS
Quantity One

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