Leptin stimulated C-reactive protein production by human coronary artery endothelial cells.
BACKGROUND
Obesity and cardiovascular disease are closely related. Leptin, an adipocyte-produced hormone, is associated with increased cardiovascular risk. Increased plasma levels of leptin are measurable in the plasma of obese individuals. However, the possible links between obesity and cardiovascular disease are not completely understood. C-reactive protein (CRP) is a predictor of future cardiovascular events and plays a role in atherothrombotic disease. Thus, we evaluated whether leptin might play a role in cardiovascular disease, investigating its effects on CRP production by human coronary artery endothelial cells in culture.


RESULTS
Leptin induced CRP mRNA transcription as demonstrated by semiquantitative and real-time polymerase chain reaction as well as the release of CRP in the culture medium in a concentration-dependent fashion. Leptin-induced production of CRP was mediated through the RhoA activation of protein kinase Cbeta since both protein kinase C and RhoA pathway inhibitors prevented these leptin effects. Lovastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, by modulating the RhoA activation, significantly reduced leptin-induced CRP production.


CONCLUSIONS
This study describes the close relationship between leptin and CRP, providing support to the view that this adipokine, besides being involved in the pathophysiology of obesity, might play a relevant role as an active partaker in obesity, inflammation and atherothrombosis.
De Rosa
Salvatore
S
Division of Cardiology, University of Naples Federico II, Naples, Italy.
Cirillo
Plinio
P
Pacileo
Mario
M
Di Palma
Vito
V
Paglia
Antonella
A
Chiariello
Massimo
M
D002070:Butadienes / Q000494:pharmacology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007211:Indoles; D020738:Leptin / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008301:Maleimides; D009570:Nitriles / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; D002070:Butadienes; D002227:Carbazoles; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D020738:Leptin; D008301:Maleimides; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C113580:U 0126; C066737:RHOA protein, human; D002097:C-Reactive Protein; D008148:Lovastatin; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D020742:rhoA GTP-Binding Protein