Leptin induces C-reactive protein expression in vascular endothelial cells.
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).


RESULTS
We confirmed the presence of both long and short isoforms of the leptin receptor in cultured HCAECs. Leptin but not IFNalphaA/D nor tumor necrosis factor (TNF) alpha, 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 micromol/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 microg/mL) prevented ERK1/2 phosphorylation and CRP mRNA transcription.


CONCLUSIONS
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.
Singh
Prachi
P
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA.
Hoffmann
Michal
M
Wolk
Robert
R
Shamsuzzaman
Abu S M
AS
Somers
Virend K
VK
D050197:Atherosclerosis / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D054411:Receptors, Leptin; D015398:Signal Transduction / Q000502:physiology*
C515448:LEPR protein, human; D020738:Leptin; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D002097:C-Reactive Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3