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Aims: Recent studies have reported that intracellular calcium (Ca2+) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na+/H+ exchanger (NHE) is responsible for an increase in the intracellular Ca2+ concentration in cardiovascular disease. We hypothesized that inhibition of the NHE had protective effects on Hcy-induced endothelial dysfunction. Methods: Acetylcholine-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in the rat isolated aorta. The level of reactive oxygen species (ROS) was designed by a specific fluorescent probe. The phosphorylation of the nuclear factor-κB (NF-κB) system was studied by Western blot. Results: Cariporide significantly prevented Hcy-impaired EDR and increased nitric oxide (NO) release; endothelial NO synthase activity simultaneously decreased ROS production. We also found that cariporide blocked Hcy-induced NF-κB activation and inhibitor-κB degradation, thus inhibiting the production of tumor necrosis factor-α and intercellular adhesion molecule-1. Conclusions: The mechanisms of protective effects of cariporide may be related to the inhibition of NHE and the decrease in oxidative stress and inflammatory injury. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: The association between diabetes and neointimal expansion after vascular injury has been attributed to the accumulation of advanced glycation end products (AGEs). Here we investigated the inhibitory effect of cariporide, a specific Na+/H+ exchanger 1 blocker, on neointimal proliferation induced by AGEs in a balloon injury model. Methods: Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP) was monitored by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. The level of reactive oxygen species (ROS) was determined by specific fluorescent probe. The phosphorylation of the nuclear factor-ĸB (NF-ĸB) system was studied by Western blot. Results: Cariporide significantly suppressed AGE-induced neointimal hyperplasia, vascular smooth muscle cell (VSMC) proliferation, COX-2, MMP-2 and MMP-9 expression. In addition, cariporide decreased AGE-induced ROS, malondiadehyde level and increased the superoxide dismutase and glutathione peroxidase activity. We also found that cariporide blocked AGE-induced NF-ĸB activation and inhibitor-ĸB degradation. Conclusions: The results indicated that cariporide inhibited AGE-induced neointimal formation by suppressing the VSMC proliferation and the up-regulation of COX-2, MMP-2, MMP-9 via inhibiting ROS and NF-ĸB activation. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Accumulation of advanced glycation end products (AGEs) plays a pivotal role in the mechanism by which aging contributes to osteoarthritis (OA). In the present study, we examined the effect of curcumin, a pharmacologically safe phytochemical agent, on AGE-induced tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-13 (MMP-13) in rabbit chondrocytes. Methods: Chondrocytes were derived from rabbit articular cartilage by enzymatic digestion. TNF-α and MMP-13 mRNA was monitored by RT-PCR. TNF-α protein was determined using cytokine-specific ELISA. The reactive oxygen species was determined by the fluorescent probe 29,79-dichlorofluorescein diacetate. The phosphorylation and nuclear translocation of the nuclear factor-ĸB (NF-ĸB) system were studied by Western blot and immunofluorescence respectively. Results: Curcumin significantly decreased AGE-stimulated TNF-α and MMP-13 mRNA and suppressed the NF-ĸB activation via inhibition of ĸBα (I-ĸBα) phosphorylation, I-ĸBα degradation and p65 nuclear translocation. Conclusions: These novel pharmacological actions of curcumin on AGE-stimulated chondrocytes provide new suggestions that curcumin has nutritional potential as a naturally occurring anti-inflammatory agent for treating OA. [ABSTRACT FROM AUTHOR]