Pro-atherothrombotic effects of leptin in human coronary endothelial cells

Plinio Cirillo; Valeria Angri; Salvatore De Rosa; Gaetano Calì; Gianluca Petrillo; Fabio Maresca; Greta-Luana D’Ascoli; Paola Maietta; Linda Brevetti; Massimo Chiariello

doi:10.1160/TH09-06-0392

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(05): 1065-1075
DOI: 10.1160/TH09-06-0392

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Pro-atherothrombotic effects of leptin in human coronary endothelial cells

Plinio Cirillo

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Valeria Angri

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Salvatore De Rosa

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Gaetano Calì

²IEOS “G. Salvatore”, National Council of Research, Naples, Italy

,

Gianluca Petrillo

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Fabio Maresca

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Greta-Luana D’Ascoli

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Paola Maietta

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Linda Brevetti

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

,

Massimo Chiariello

¹Department of Clinical Medicine, Cardiovascular and Immunological Science (Division of Cardiology), University of Naples “Federico II”, Naples, Italy

› Author Affiliations

Abstract

Summary

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-κB, since L-NAME, Superoxide Dismutase and NF-κB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro, indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Keywords

Adhesion molecules - adipokines - atherothrombosis - leptin - obesity - tissue factor

Full Text

References

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