Lysophosphatidic Acid: A Novel Phospholipid with Hormone- and Growth Factor-like Activities

Moolenaar, Wouter H.; Bend, R L van der; Corven, E J van; Jalink, Kees; Eichholtz, Thomas; Blitterswijk, Wim J. van

doi:10.1101/sqb.1992.057.01.021

Cited by 20 publications

(22 citation statements)

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“…LPA-dependent signaling in cells occurs through heterotrimeric G-linked protein signaling pathways (Moolenar, 1995;Moolenar et al, 1992). LPA treatment of cells has been demonstrated to activate or inhibit at least four G-protein-linked signaling pathways in cells.…”

Section: Introductionmentioning

confidence: 99%

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Spencer

Misra

1999

Oncogene

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Section: Introductionmentioning

confidence: 99%

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Spencer

Misra

1999

Oncogene

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“…[1][2][3] Some of the earliest observations of receptormediated actions of LPA came from studies in platelets. 4 -7 LPA stimulates platelet shape change, 6,8 fibronectin matrix assembly, 9 and platelet-monocyte coaggregate formation.…”

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confidence: 99%

Individual Heterogeneity in Platelet Response to Lysophosphatidic Acid

Pamuklar

Lee

Cheng

et al. 2008

ATVB

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Objective-The bioactive lipid lysophosphatidic acid (LPA) stimulates platelet actin reorganization, adhesion, shape change, and aggregation. LPA is present in blood and exposure or release of LPA after atherosclerotic plaque rupture has been proposed to trigger platelet thrombus formation. Methods and Results-In this report, we characterize heterogeneity in LPA responses among individuals. Platelets isolated from approximately 20% of healthy donors consistently failed to aggregate in response to LPA. Our studies indicate that, rather than lacking stimulatory pathways, platelets from "nonresponsive" donors respond to LPA by triggering inhibitory pathway(s) to block platelet aggregation. Consistent with this observation, LPA-induced aggregation could be partially restored to "nonresponsive" platelets by pharmacological inhibition of cAMP generation. LPA "nonresponsiveness" may be related to heightened platelet expression of LPA receptor 4 and PPAR␥. Among 70 patients with stable coronary artery disease (CAD), only 1 (1.4%) was identified as an LPA nonresponder. Moreover, in 33 patients presenting for diagnostic catheterization, CAD was identified as having a bivariate association with platelet LPA responder/nonresponder status. Conclusions-Platelet

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“…The bioactive lipid mediator lysophosphatidic acid (1-acylsn-glycero-3-phosphate or LPA) 3 is poised to serve an important role in the development and complications of atherothrombosis (1,2). The exposure of human platelets to LPA triggers shape change (3)(4)(5), fibronectin matrix assembly (6), and platelet-leukocyte interactions (7).…”

mentioning

confidence: 99%

Autotaxin/Lysopholipase D and Lysophosphatidic Acid Regulate Murine Hemostasis and Thrombosis

Pamuklar

Federico

Liu

et al. 2009

Journal of Biological Chemistry

132

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The lipid mediator lysophosphatidic acid (LPA) is a potent regulator of vascular cell function in vitro, but its physiologic role in the cardiovasculature is largely unexplored. To address the role of LPA in regulating platelet function and thrombosis, we investigated the effects of LPA on isolated murine platelets. Although LPA activates platelets from the majority of human donors, we found that treatment of isolated murine platelets with physiologic concentrations of LPA attenuated agonist-induced aggregation. Transgenic overexpression of autotaxin/lysophospholipase D (Enpp2), the enzyme necessary for production of the bulk of biologically active LPA in plasma, elevated circulating LPA levels and induced a bleeding diathesis and attenuation of thrombosis in mice. Intravascular administration of exogenous LPA recapitulated the prolonged bleeding time observed in Enpp2-Tg mice. Enpp2 ؉/؊ mice, which have ϳ50% normal plasma LPA levels, were more prone to thrombosis. Plasma autotaxin associated with platelets during aggregation and concentrated in arterial thrombus, and activated but not resting platelets bound recombinant autotaxin/ lysoPLD in an integrin-dependent manner. These results identify a novel pathway in which LPA production by autotaxin/lysoPLD regulates murine hemostasis and thrombosis and suggest that binding of autotaxin/lysoPLD to activated platelets may provide a mechanism to localize LPA production.

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Lysophosphatidic Acid: A Novel Phospholipid with Hormone- and Growth Factor-like Activities

Cited by 20 publications

References 0 publications

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Individual Heterogeneity in Platelet Response to Lysophosphatidic Acid

Autotaxin/Lysopholipase D and Lysophosphatidic Acid Regulate Murine Hemostasis and Thrombosis

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