Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects.

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Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR, Coleman CN

Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects.

J Cardiovasc Pharmacol. 2012 Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5.

PubMed ID

22668799 [ View in PubMed

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal, and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in the clinic. Coronary artery smooth muscle cells and endothelial cells were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib, NS398, and ibuprofen for 24 hours. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time reverse-transcription polymerase chain reaction and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis. At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease, and hypertension. The gene expression was most impacted by ibuprofen, celecoxib, and NS398, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dexibuprofen	Apoptosis regulator Bcl-2	Protein	Humans	Unknown	Negative modulator	Details
Dexibuprofen	Platelet glycoprotein Ib alpha chain	Protein	Humans	Unknown	Not Available	Details
Dexibuprofen	Thrombomodulin	Protein	Humans	Unknown	Modulator	Details
Ibuprofen	Apoptosis regulator Bcl-2	Protein	Humans	Unknown	Modulator	Details
Ibuprofen	Platelet glycoprotein Ib alpha chain	Protein	Humans	Unknown	Inducer	Details
Ibuprofen	Thrombomodulin	Protein	Humans	Unknown	Inducer	Details