PMID- 19387587 OWN - NLM STAT- MEDLINE DCOM- 20090520 LR - 20090423 IS - 0253-6269 (Print) IS - 0253-6269 (Linking) VI - 32 IP - 3 DP - 2009 Mar TI - A novel in vitro ischemia/reperfusion injury model. PG - 421-9 LID - 10.1007/s12272-009-1316-9 [doi] AB - The reperfusion of blood flow occurred in a number of conditions such as stroke and organ transplantation immensely augments tissue injury and causes more severe damage than prolonged ischemia. In the present study, we designed a novel double-layer parallel-plate flow chamber (PPFC) to develop an in vitro ischemia/reperfusion (I/R) injury model and examined the effects of I/R on inflammatory responses in human microvascular endothelial cells (HMEC-1). The expression of pro-inflammatory mediators, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in HMEC-1 was measured by quantitative real-time RT-PCR. The cells were also pre-treated with antioxidant pyrrolidine dithiocarbamate (PDTC) to verify involvement of an oxidative mechanism in I/R injury in vitro. The morphological changes and attenuated expression of pro-inflammatory mediators were observed in HMCE-1 exposed to the physiological flow. In contrast, I/R markedly and significantly up-regulated expression of pro-inflammatory mediators in HMEC-1. Additionally, pretreatment with PDTC significantly reduced I/R-mediated overexpression of pro-inflammatory mediators. The data from the present study provide evidence demonstrating that our newly designed PPFC can be utilized as an effective in vitro cell culture model system to develop new drugs specifically targeting against ischemia/reperfusion (I/R) injury. FAU - Lee, Won Hee AU - Lee WH AD - School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA 24061, USA. FAU - Kang, Sungkwon AU - Kang S FAU - Vlachos, Pavlos P AU - Vlachos PP FAU - Lee, Yong Woo AU - Lee YW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090423 PL - Korea (South) TA - Arch Pharm Res JT - Archives of pharmacal research JID - 8000036 RN - 0 (Antioxidants) RN - 0 (Inflammation Mediators) RN - 0 (Pyrrolidines) RN - 0 (Thiocarbamates) RN - 25769-03-3 (pyrrolidine dithiocarbamic acid) SB - IM MH - Antioxidants/pharmacology MH - *Cell Culture Techniques MH - Cell Shape MH - Cells, Cultured MH - Endothelial Cells/drug effects/*metabolism MH - Gene Expression Regulation MH - *Hemorheology MH - Humans MH - Inflammation/genetics/*metabolism/physiopathology MH - Inflammation Mediators/*metabolism MH - Microcirculation MH - Oxidative Stress MH - Pyrrolidines/pharmacology MH - Regional Blood Flow MH - Reperfusion Injury/genetics/*metabolism/physiopathology MH - Stress, Mechanical MH - Thiocarbamates/pharmacology MH - Time Factors MH - Up-Regulation EDAT- 2009/04/24 09:00 MHDA- 2009/05/21 09:00 CRDT- 2009/04/24 09:00 PHST- 2008/11/12 00:00 [received] PHST- 2009/03/06 00:00 [accepted] PHST- 2009/03/04 00:00 [revised] PHST- 2009/04/24 09:00 [entrez] PHST- 2009/04/24 09:00 [pubmed] PHST- 2009/05/21 09:00 [medline] AID - 10.1007/s12272-009-1316-9 [doi] PST - ppublish SO - Arch Pharm Res. 2009 Mar;32(3):421-9. doi: 10.1007/s12272-009-1316-9. Epub 2009 Apr 23.