A profile of NSAID-targeted arachidonic acid metabolisms in human embryonic stem cells (hESCs): Implication of the negative effects of NSAIDs on heart tissue regeneration

作者：Chillar Annirudha; So Shui Ping; Ruan Cheng Huai; Shelat Harnath; Geng Yong Jian^*; Ruan Ke He

来源：International Journal of Cardiology, 2011, 150(3): 253-259.

DOI：10.1016/j.ijcard.2010.04.015

• Human embryonic stem cells
• NSAIDs
• Cyclooxygenase
• Arachidonic acid
• Prostacyclin
• COX-2 inhibitor

Introduction: An emerging technology using human embryonic stem cells (hESCs) to regenerate infarcted heart tissue has been underdeveloped. However, because non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are taken during the infarction, it becomes critical to know whether the NSAIDs have negative impacts on heart tissue regeneration when using hESCs.
Methods: Mass spectrometry (LC/MS/MS) and high performance liquid chromatography (HPLC) analyses were used to analyze the functional presence of the elaborate prostanoids' biosynthesis and signaling systems in hESCs. The detected endogenous arachidonic acid (AA) released in the hESC membranes reflects the activity of phospholipase which directly controls the biosyntheses of the prostanoids.
Results: The complete inhibition of the endogenous prostaglandin E(2) (PGE(2)) biosynthesis by the cyclooxygenase-2 (COX-2) inhibitor, NS398, confirmed that the major prostanoids synthesized in the hESCs are mediated by the COX-2 enzyme. We also found that PGE(2) and the prostacyclin (PGI(2)) metabolite, 6-keto-PGF(1 alpha), are present in the undifferentiated hESCs.
Conclusion: This indicated different cyclooxygenase (COX)-downstream synthases and metabolizing enzymes are involved in the AA products' signaling through the COX-1 and COX-2 pathways. The presence of many enzymes' and receptors' [(COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), cytosolic prostaglandin E synthase (cPGES), prostaglandin I synthase (PGIS), the PGE(2) subtype receptors (EP(1), EP(2), and EP(4)) and the prostacyclin receptor (IP)] involvement in the prostanoid biosynthesis and activity was confirmed by western blot. The studies implied the negative effects of NSAIDs, such as aspirin and COX-2 inhibitors, which suppress prostanoid production during tissue regeneration for infarcted heart when using hESCs.

• 出版日期2011-8-4