Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration

Qingjie Wang, Leijun Huo, Jinlong He, Wenshuang Ding, Hang Su, Dongping Tian, Carrie Welch, Bruce D. Hammock, Ding Ai, Yi Zhu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing their biological activity. sEH inhibitors can suppress the progression of atherosclerotic lesions in animal models. However, the regulation of sEH in vascular smooth muscle cells (VSMCs) and role of sEH in patients with atherosclerosis have not been evaluated. We hypothesize that sEH in VSMCs plays a pivotal role in atherosclerosis and injury-induced neointima formation. In this study, sEH expression in human autopsy atherosclerotic plaque was determined by immunohistochemistry. In cultured rat and human VSMCs, the phenotypic switching marker and sEH expression induced by plateletderived growth factor-BB (PDGF-BB) were examined by Western blot analysis. Carotid-artery balloon injury was performed after adenovirus- mediated overexpression of sEH or oral administration of a potent sEH inhibitor in Sprague-Dawley rats. sEH was highly expressed in VSMCs of the intima and media within human atherosclerotic plaque. In vitro, PDGF-BB upregulated the expression in VSMCs after transcription and promoted cell proliferation and migration; the latter effect could be largely attenuated by an sEH inhibitor. Adenovirus-mediated overexpression of sEH could mimic the effect of PDGF-BB and induce VSMC proliferation and migration. In vivo, the sEH inhibitor led to a significant decrease in injury-induced neointima formation in a rat carotid-artery injury model. These data establish the effect of sEH expression on atherosclerotic progression and vascular remodeling after injury, thus identifying a novel integrative role for sEH in VSMC phenotypic modulation and migration. Blocking sEH activity may be a potential therapeutic approach for ameliorating vascular occlusive disease.

Original languageEnglish (US)
Pages (from-to)H1894-H1903
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number11
DOIs
StatePublished - 2015

Fingerprint

Epoxide Hydrolases
Neointima
Smooth Muscle Myocytes
Cell Movement
Atherosclerosis
Vascular Smooth Muscle
Carotid Artery Injuries
Intercellular Signaling Peptides and Proteins
Atherosclerotic Plaques
Adenoviridae
Wounds and Injuries
Cell Proliferation

Keywords

  • Atherosclerosis
  • Migration
  • Neointima formation
  • Soluble epoxide hydrolase inhibitor
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration. / Wang, Qingjie; Huo, Leijun; He, Jinlong; Ding, Wenshuang; Su, Hang; Tian, Dongping; Welch, Carrie; Hammock, Bruce D.; Ai, Ding; Zhu, Yi.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 309, No. 11, 2015, p. H1894-H1903.

Research output: Contribution to journalArticle

Wang, Qingjie ; Huo, Leijun ; He, Jinlong ; Ding, Wenshuang ; Su, Hang ; Tian, Dongping ; Welch, Carrie ; Hammock, Bruce D. ; Ai, Ding ; Zhu, Yi. / Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration. In: American Journal of Physiology - Heart and Circulatory Physiology. 2015 ; Vol. 309, No. 11. pp. H1894-H1903.
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AU - Wang, Qingjie

AU - Huo, Leijun

AU - He, Jinlong

AU - Ding, Wenshuang

AU - Su, Hang

AU - Tian, Dongping

AU - Welch, Carrie

AU - Hammock, Bruce D.

AU - Ai, Ding

AU - Zhu, Yi

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