C.K. Oh, M.S.F. Ahmed, C. Xie, J.H. Ryu, J. Choi, J.S. Chung, G.S. Roh, H.J. Kim, G.J. Cho, W.S. Choi, S.S. Kang, D.H. Lee
Published: December 13, 2018
Genet. Mol. Res. 17(4): GMR18068
DOI: https://doi.org/10.4238/gmr18068
Cite this Article:
C.K. Oh, M.S.F. Ahmed, C. Xie, J.H. Ryu, J. Choi, J.S. Chung, G.S. Roh, H.J. Kim, G.J. Cho, W.S. Choi, S.S. Kang, D.H. Lee (2018). Microarray analysis of NSAIDs-treated cardiomyocytes to search for genes involved in COX-2 inhibitor cardiotoxicity. Genet. Mol. Res. 17(4): GMR18068. https://doi.org/10.4238/gmr18068
About the Authors
C.K. Oh, M.S.F. Ahmed, C. Xie, J.H. Ryu, J. Choi, J.S. Chung, G.S. Roh, H.J. Kim, G.J. Cho, W.S. Choi, S.S. Kang, D.H. Lee
Corresponding Author
D.H. Lee
Email: bx113@gnu.ac.kr
ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely-used medications for the treatment of many inflammatory diseases. . They inhibit cyclooxygenase (COX) enzymes as a primary mechanism of action. However, many of these drugs were withdrawn from the market because of cardiovascular side effects. To date, only a limited number of genes and specific gene variants that account for their cardiac toxicity have been investigated. To identify possible cardiotoxic effects, we performed a microarray analysis of NSAIDs-treated primary cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were established and a DNA microarray was run on extracted RNA from celecoxib and diclofenac-treated cardiomyocytes. The changes in gene expression for all potentially predisposing variants were investigated. In cells treated with celecoxib, the expression of 1718 and 560 genes decreased and increased respectively by 2-fold or more. When cells were treated with diclofenac, the expression of 424 and 32 genes decreased and increased respectively by 2-fold or more. NSAIDs affected the expression of genes involved in calcium and potassium signaling. Pathway analysis of gene expression of NSAIDs-treated cardiomyocytes showed changes in gene expression involving major pathways, including apoptosis, signal transduction and transcription. These findings provide a clue to explain, at least in part, how NSAIDs provoke side effects in the heart. These data could be used to elect target genes for studying cardiotoxic effects of NSAIDs and for developing new drugs.
Key words: Cardiotoxicity, Celecoxib, Diclofenac, EC decoupling, Microarray, NSAIDs.