Vascular remodeling induced by naturally occurring unsaturated lysophosphatidic acid in vivo

Kenji Yoshida, Wataru Nishida, Ken'ichiro Hayashi, Yasuyuki Ohkawa, Akira Ogawa, Junken Aoki, Hiroyuki Arai, Kenji Sobue

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Background - We previously identified unsaturated (16:1, 18:1, and 18:2) but not saturated (12:0, 14:0, 16:0, and 18:0) lysophosphatidic acids (LPAs) as potent factors for vascular smooth muscle cell (VSMC) dedifferentiation. Unsaturated LPAs strongly induce VSMC dedifferentiation via the coordinated activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK), resulting in the proliferation and migration of dedifferentiated VSMCs. Here, we investigated the effects of 18:1 and 18:0 LPAs (as representative unsaturated and saturated LPAs, respectively) on the vasculature in vivo. Methods and Results - Rat common carotid arteries (CCAs) were treated transiently with 18:1 or 18:0 LPA and then examined by histological and biochemical analyses. The 18:1 but not 18:0 LPA potently induced vascular remodeling that was composed primarily of neointima. The incorporation of [3H]18:1 LPA into the CCAs revealed that a sufficient amount of unmetabolized [3H]18:1 LPA to induce VSMC dedifferentiation was present in the vascular wall. The 18:1 LPA-induced neointimal formation in vivo was also dependent on the coordinated activation of ERK and p38MAPK. Unlike balloon-injured CCAs, the 18:1 LPA-treated CCAs showed a histological similarity to human atherosclerotic arteries. Conclusions - This is the first report demonstrating a role for a naturally occurring unsaturated LPA in inducing vascular remodeling in vivo and provides a novel animal model for neointimal formation.

Original languageEnglish
Pages (from-to)1746-1752
Number of pages7
JournalCirculation
Volume108
Issue number14
DOIs
Publication statusPublished - Oct 7 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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