Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta

Abstract

Lysophosphatidic acids (LPA) with a C18 fatty acyl group accelerated thymidine incorporation into cultured rat aortic vascular smooth muscle cells and stimulated their cell division. LPA acted synergistically with epidermal growth factor and fibroblast growth factor but additively with platelet-derived growth factor. The stimulatory actions of LPA were suggested to be rather specific from the following findings: 1) their stimulation of DNA synthesis increased with an increase in their acyl moiety; 2) lysophosphatidylcholine, a neutral lysophospholipid, had no mitogenic action but was cytotoxic at high concentrations; and 3) LPA induced a rapid external Ca(2+)-independent increase in intracellular Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells that resembled the receptor-mediated increases in [Ca2+]i triggered by different agonists, whereas lysophosphatidylcholine provoked a slow sustained increase in [Ca2+]i in an external Ca(2+)-dependent manner. These results are discussed in relation to the possible pathophysiological role of LPA.

Serum bioactive lysophospholipids prevent TRAIL-induced apoptosis via PI3K/Akt-dependent cFLIP expression and Bad phosphorylation

“…These concentrations are pathophysiologically relevant, since their levels in serum range from 2 to 28 and 0.2 to 0.5 mM, respectively. 48,49 Since LPA concentrations attaining 28 mM were reported in FBS, 50 medium containing 10% FBS used in this study was equal to 2.8 mM of LPA, which significantly protected cells from TRAILinduced apoptosis (Figure 1). However, plasma levels of LPA from healthy individuals are relatively low, approximately 0.5 mM.…”

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

“…LPA is a mitogen to subcultured VSMC [50]. It has also been reported that unsaturated species of LPA present in serum promote PM in cultured VSMC [42].…”

“…LPA has not only been implicated in PM but also in normal vascular development [49], SMC and VSMC mitogenesis [50,51], and contractility [52,53]. Alkyl-LPA has been identified as a biologically active lipid in mildly oxidized low-density lipoprotein, human atherosclerotic lesions, and the supernatant of activated platelets [54].…”

Molecular Cloning and Characterization of a Novel Human G-protein-coupled Receptor, EDG7, for Lysophosphatidic Acid

“…It has been previously demonstrated that LPAs with unsaturated fatty acids evoked greater Ca 2ϩ responses of the human epidermoid carcinoma cell line A431 than LPAs with saturated fatty acids (30). In addition, Tokumura et al (31) reported that degree of unsaturation in the acyl moiety of LPA affects proliferation of cultured vascular smooth muscle cells from rat aorta by LPA. A newly identified LPA receptor, EDG7, may account for these response.…”