Pharmacological regulation of low density lipoprotein receptor expression: Current status and future developments

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Plasma levels of low-density lipoprotein (LDL) cholesterol are considered to be a major risk factor for the development of cardiovascular diseases. The LDL receptor is the key component in the maintenance of cholesterol homeostasis in the body, playing a pivotal role by regulating the hepatic catabolism of LDL cholesterol. Many clinical studies using statins, which up-regulate the LDL receptor expression via a feedback mechanism, have demonstrated that the reduction of LDL cholesterol levels lowers the incidence of cardiovascular events in both primary and secondary prevention. In this context, new strategies designed to increase hepatic LDL receptor activity can be considered as attractive opportunities for future therapy. Several potential new drugs have been described in the last decade to up-regulate LDL receptor expression in vitro and in vivo, thus allowing the identification of new transcriptional and post-transcriptional mechanisms.

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