Effects of phosphodiesterase inhibitors on the inflammatory response of endothelial cells stimulated by myeloperoxidase-modified low-density lipoprotein or tumor necrosis factor alpha
Abstract
BACKGROUND: Sildenafil, vardenafil, and tadalafil are phosphodiesterase type 5 inhibitors (PDE5-Is) usually used in the treatment of erectile dysfunction (ED). Previously, we have shown the presence of myeloperoxidase-modified low-density lipoprotein (Mox-LDL) in the penises of patients with ED, and we have shown the impact of Mox-LDL on cyclic monophosphate (cGMP) level. In vitro, Mox-LDL triggered the inflammatory response by increasing the release of both interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) by endothelial cells (ECs) and monocytes respectively.
OBJECTIVE: To determine whether or not the three therapeutically PDE5-Is protect against the proinflammatory effects of Mox-LDL or TNF-alpha on ECs.
DESIGN, SETTING, AND PARTICIPANTS: ECs (EA.hy926) were incubated in the presence of either TNF-alpha (100 pg/ml) or Mox-LDL (200 microg/ml) with each of the three PDE5-Is (1 microM, 5 microM, and 10 microM) respectively. IL-8 production was measured in the supernatant after 48 h of incubation.
MEASUREMENTS: All experiments were repeated at least three times. Statistical analysis was performed with an ANOVA.
RESULTS AND LIMITATIONS: Two-way ANOVA analysis showed that TNF-alpha alone (p<0.001) or Mox-LDL alone (p<0.001) increased IL-8 production. Sildenafil, vardenafil, or tadalafil alone did not generate an increase of IL-8 production. Tadalafil in combination with Mox-LDL and TNF-alpha showed a decrease of IL-8 (p<0.05) compared with sildenafil and…
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