Leptin induces C-reactive protein expression in vascular endothelial cells

Prachi Singh, Michal Hoffmann, Robert Wolk, Abu S.M. Shamsuzzaman, Virend K. Somers

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

OBJECTIVE - There is increasing evidence of an association between leptin and increased cardiovascular risk. Higher leptin levels are associated with increased levels of C-reactive protein (CRP), which itself elicits proatherogenic effects in the vascular endothelium. We tested the hypothesis that leptin induces CRP expression in human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS - We confirmed the presence of both long and short isoforms of the leptin receptor in cultured HCAECs. Leptin but not IFNαA/D nor tumor necrosis factor (TNF) α, induced expression of CRP. A dose dependent increase of CRP mRNA and protein was observed with increasing concentration of leptin (0 to 400 ng/mL). This increased CRP expression was attenuated in the presence of anti-leptin receptor antibodies and also by inhibition of ERK1/2 by PD98059 (20 to 40 μmol/L). Time (0 to 60 minutes) and leptin concentration (0 to 200 ng/mL)-dependence of ERK1/2 phosphorylation were evident in response to leptin treatment. Leptin also elicited ROS generation. Inhibition of ROS by catalase (200 μg/mL) prevented ERK1/2 phosphorylation and CRP mRNA transcription. CONCLUSION - Leptin induces CRP expression in HCAECs via activation of the leptin receptor, increased ROS production, and phosphorylation of ERK1/2. These studies suggest a mechanism for the proatherogenic effects of leptin.

Original languageEnglish (US)
Pages (from-to)e302-e307
JournalArteriosclerosis, thrombosis, and vascular biology
Volume27
Issue number9
DOIs
StatePublished - Sep 2007

Keywords

  • Atherosclerosis
  • C-reactive protein
  • Endothelium
  • Leptin
  • Obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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