Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects

• Published in: Cardiovascular therapeutics 2017-08, Vol.35 (4), p.n/a
• Main Authors: Cerda, Alvaro, Pavez, Monica, Manriquez, Victor, Luchessi, Andre Ducati, Leal, Pamela, Benavente, Felipe, Fajardo, Cristina Moreno, Salazar, Luis, Hirata, Mario Hiroyuki, Hirata, Rosario Dominguez Crespo
• Format: Article
• Language: English
• Subjects: Adhesion molecules; Cell Adhesion Molecules - biosynthesis; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Clopidogrel; Cytokines - biosynthesis; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Gene expression; Gene Expression Regulation - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inflammation; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Synthase Type III - biosynthesis; Nitric Oxide Synthase Type III - genetics; Platelet Aggregation Inhibitors - pharmacology; Pleiotropic effects; Protein expression; Proteins; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology
• ISSN: 1755-5914; 1755-5922
• DOI: 10.1111/1755-5922.12261

Summary Introduction Clopidogrel is commonly used in prevention and treatment of atherothrombosis. Some previous studies have suggested a pleiotropic effect of clopidogrel; however, when this drug causes platelet‐independent effects on endothelial function remains unclear. Aims To evaluate the influence of clopidogrel on inflammatory biomarkers and adhesion molecules in human endothelial cells and the role of nitric oxide (NO) in this process. Methods TNF‐α‐induced human umbilical vein endothelial cells (HUVEC) were exposed to clopidogrel. Gene expression and protein expression of ICAM‐1, P‐selectin, IL‐8, IL‐6, and MCP‐1 were evaluated by qPCR, flux cytometry, or milliplex technology. Expression of endothelial nitric oxide synthase (NOS3) and NO release were also evaluated. Influence of clopidogrel was further evaluated in NOS3 downregulated HUVEC by RNAi. Results Clopidogrel at 20 μmol/L induced NO release in HUVEC after 24‐hours treatment. Gene expressions of inflammatory markers IL‐8 and MCP1 were reduced after clopidogrel treatment (P