Hypertriglyceridemia Therapy: Past, Present and Future Perspectives

Figures

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  Figure 1. Evidence of fenofibrate-induced side effects on skeletal muscle function collected by previous studies [11]. (A) Fenofibrate administered in vivo to rats reduced the resting chloride conductance (gCl) sustained by the ClC-1 chloride channel in the extensor digitorum longus fast-twitch muscle. This effect is responsible for sarcolemma instability. Since ClC-1 is negatively modulated by protein kinase C (PKC), we evaluated the effects of the in vitro application of chelerythrine, an inhibitor of this protein. Chelerythrine did not restore gCl, suggesting that the reduction in gCl is not mediated by PKC activation but is a direct inhibitory effect on the channel. # Significantly different with respect to control (CTRL) value measured in physiological solution (by Student’s t-test) (p < 0.001) [11]. (B) Fenofibrate increased sarcolemma excitability, evidenced by the increase in the maximum number of spikes in rat skeletal muscle fibres [11]. (C) Effect of in vitro application of fenofibric acid on hClC-1 channel expression in cultured HEK293 cells. Whole-cell patch-clamp chloride currents were recorded in the absence and presence of 500 μM of fenofibric acid. Fenofibric acid…

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  Figure 2. Description of recent therapeutic approaches that are useful for reducing hypertriglyceridemia, a disease that can be responsible for the progression of cardiovascular diseases. The drugs (already used in therapy or in clinical trial evaluations) are classified based on their mechanisms of action. See text for details. ASO: antisense oligonucleotides; MoAb: monoclonal antibody; FGF21: human fibroblast growth factor 21.