PMID- 17261959 OWN - NLM STAT- MEDLINE DCOM- 20070327 LR - 20131121 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 49 IP - 1 DP - 2007 Jan TI - Impact of simvastatin and losartan on antiinflammatory effect: in vitro study. PG - 20-6 AB - Antiinflammatory properties of losartan are currently unclear. This study tested the hypothesis that losartan itself has an antiinflammatory effect comparable to that of simvastatin. Human umbilical vein endothelial cells (HUVECs) were (1) incubated with culture medium alone, (2) incubated with added C-reactive protein (CRP) (25, 50, 75, and 100 microg/mL) for stimulation, and (3) pretreated with losartan (stepwise increased dose: 100, 300, 500, and 750 micromol/L) and simvastatin (stepwise increased dose: 25, 50, 75, and 100 micromol/L) for 4 hours before adding CRP for stimulation. Surface expression of vascular cell adhesion molecule-1 (VCAM-1) was determined by flow cytometry. Supernatant levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) were measured by ELISA. Experimental results showed that the effect of CRP on VCAM-1 expression and supernatant levels of MCP-1 and IL-6 increases stepwise as CRP concentrations increase from 25 to 50 to 75 to 100 microg/mL (all P < 0.001). The effect of CRP on VCAM-1 expression in HUVECs and supernatant levels of MCP-1 and IL-6 were significantly suppressed by 25 micromol/L simvastatin with stepwise increased suppression as simvastatin dose increased to 50, 75, and 100 micromol/L (all P < 0.0001). However, losartan did not significantly suppress CRP's effect on VCAM-1 expression in HUVECs (P > 0.5). Moreover, losartan did not suppress CRP's effect on MCP-1 and IL-6 secretion unless a high dose (> or =500 micromol/L) of losartan was used. Compared with simvastatin, losartan had less effect on suppression of CRP-mediated inflammation. FAU - Chang, Li-Teh AU - Chang LT AD - Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung, Taiwan, ROC. FAU - Sun, Cheuk-Kwan AU - Sun CK FAU - Chiang, Chiang-Hua AU - Chiang CH FAU - Wu, Chiung-Jen AU - Wu CJ FAU - Chua, Sarah AU - Chua S FAU - Yip, Hon-Kan AU - Yip HK LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Anticholesteremic Agents) RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 9007-41-4 (C-Reactive Protein) RN - AGG2FN16EV (Simvastatin) RN - JMS50MPO89 (Losartan) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/*pharmacology MH - Anti-Inflammatory Agents, Non-Steroidal/*metabolism/pharmacology MH - Anticholesteremic Agents/*pharmacology MH - C-Reactive Protein/*physiology MH - Cells, Cultured MH - Endothelial Cells/*drug effects/metabolism/pathology MH - Endothelium, Vascular/drug effects/metabolism/pathology MH - Humans MH - Losartan/*pharmacology MH - Receptor, Angiotensin, Type 1/biosynthesis/genetics MH - Simvastatin/*pharmacology MH - Vascular Cell Adhesion Molecule-1/biosynthesis/drug effects/genetics EDAT- 2007/01/31 09:00 MHDA- 2007/03/28 09:00 CRDT- 2007/01/31 09:00 PHST- 2007/01/31 09:00 [pubmed] PHST- 2007/03/28 09:00 [medline] PHST- 2007/01/31 09:00 [entrez] AID - 00005344-200701000-00004 [pii] AID - 10.1097/FJC.0b013e31802ba4ec [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2007 Jan;49(1):20-6. doi: 10.1097/FJC.0b013e31802ba4ec.