Abstract 356: Torcetrapib and Dalcetrapib, CETP inhibitors, Induce Adipocyte-derived Aldosterone and Reactive Oxygen Species Formation
| Autor: | Francisco J Rios, Aurelie Nguyen Dinh Cat, Roberto Palacios, Andrew Carswell, Augusto C Montezano, Rhian M Touyz |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Hypertension. 62 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Hyperaldosteronism and hypertension were major side effects observed in clinical trials with Torcetrapib (TORC), a CETP inhibitor that increases HDL. Reasons for this are unclear. Given that CETP inhibitors accumulate in adipose tissue and that adipocytes are a source of aldosterone, we questioned whether CETP inhibitors, TORC and Dalcetrapib (DALC), influence adipocyte aldosterone production. Putative mechanisms underlying this were also explored. Human adipocytes, expressing CETP were studied and compared to mouse adipocytes, which lack CETP gene. Human SW872 and 3T3-L1 adypocites were treated with TORC and DALC (1-30 μM). Reactive Oxygen Species (ROS) production was evaluated by lucigenin-enhanced chemiluminescence. Aldosterone levels were evaluated by ELISA. Gene expression for Mineralocoricoid Receptor (MR), PPARγ, aldosterone synthase (CYP11B2) and glucorticoid synthase (CYP11B1) were evaluated by real time PCR. In human adipocytes, TORC and DALC induced 2- and 1.5-fold increase respectively in ROS production after 5 min (p |
| Databáze: | OpenAIRE |
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