The adipokine visfatin induces tissue factor expression in human coronary artery endothelial cells: another piece in the adipokines puzzle.
BACKGROUND
Adipocytes are nowadays recognized as cells able to produce and secrete a large variety of active substances with direct effects on vascular cells, known as adipokines. Visfatin is a recently identified adipokine not yet completely characterized for its pathophysiological role in cardiovascular disease. Increased levels of visfatin are measurable in the plasma of patients with coronary artery disease and specifically in those with acute coronary syndromes (ACS). Several studies have indicated that Tissue Factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of visfatin on TF in human coronary endothelial cells (HCAECs).


METHODS
HCAECs were stimulated with visfatin in a concentration range usually measurable in plasma of patients with ACS and than processed to evaluate TF-mRNA levels as well as TF expression/activity. Finally, the role of NF-κB pathway was investigated.


RESULTS
We demonstrate that visfatin induces transcription of mRNA for TF by Real Time PCR. In addition, we show that this adipokine promotes surface expression of TF that is functionally active since we measured increased procoagulant activity. Visfatin effects on TF appear modulated by the activation of the transcription factor, NF-κB, since NF-κB inhibitors suppressed TF expression. Finally, we show that the nicotinamide phopsphoribosyltransferase enzymatic activity of visfatin seems to play a pivotal role in modulating the NF-κB driven regulation of TF.


CONCLUSIONS
Data of the present study, although in vitro, indicate that visfatin, at doses measurable in ACS patient plasma, induces a procoagulant phenotype in human coronary endothelial cells by promoting TF expression. These observations support the hypothesis that this adipokine might play a relevant role as an active partaker in athero-thrombotic disease.
Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Via Sergio Pansini 5, 80131 Naples, Italy. pcirillo@unina.it
Plinio
P
Cirillo
Vito
V
Di Palma
Fabio
F
Maresca
Francesco
F
Pacifico
Francesca
F
Ziviello
Michele
M
Bevilacqua
Bruno
B
Trimarco
Antonio
A
Leonardi
Massimo
M
Chiariello
D054392:Adipokines / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000008:administration & dosage* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016328:NF-kappa B / Q000276:immunology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000008:administration & dosage* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013925:Thromboplastin / Q000276:immunology*
D054392:Adipokines; D016207:Cytokines; D016328:NF-kappa B; D013925:Thromboplastin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human