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New lipid-lowering agents acting on LDL receptors.
Curr Top Med Chem. 2005; 5(3):233-42.CT

Abstract

The treatment of dyslipoproteinemia has proven a successful strategy in the prevention of cardiovascular diseases. The major target of hypolipidemic drugs is the reduction of low density lipoprotein cholesterol (LDL-C). HMG-CoA reductase inhibitors (HMGRI) effectively lower LDL-C by inhibiting the mevalonate pathway and enhancing the activity of the LDL receptor (LDL-R). Numerous clinical studies demonstrated convincingly, that the reduction of LDL-C lowers the incidence of cardiovascular events in primary and secondary prevention. Two new HMGRI, rosuvastatin and pitavastatin, have been evaluated in clinical trials. Both drugs demonstrated efficacy in lowering atherogenic lipoproteins. In addition to the reduction of LDL-C, they may have a higher potency to lower triacylglycerides (TG) and to increase HDL cholesterol (HDL-C) compared to currently available HMGRI. Other therapeutic strategies examined in experimental animals are the inhibition of squalene synthase, the first enzyme of the mevalonate pathway, which is specifically committed to cholesterol biosynthesis, and the direct up-regulation of LDL receptor activity. The latter compounds, the SCAP ligands, are the first members of a new class of hypolipidemic agents affecting the transcriptional regulation of genes involved in lipid metabolism. Recent treatment guidelines emphasise the importance of modifying lipid metabolism beyond lowering LDL-C, mainly by lowering TG and raising HDL-C. Although these actions are not primary targets of the compounds discussed here, it is interesting that drugs inducing the LDL-R usually also lower TG and, in the case of HMGRI, increase HDL-C.

Authors+Show Affiliations

Clinical Institute of Medical and Clinical Laboratory Diagnositcs, Medical University, Auenbruggerplatz 15, A-8036 Graz, Austria. hubert.scharnagl@klinikum-graz.atNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Review

Language

eng

PubMed ID

15857307

Citation

Scharnagl, Hubert, and Winfried März. "New Lipid-lowering Agents Acting On LDL Receptors." Current Topics in Medicinal Chemistry, vol. 5, no. 3, 2005, pp. 233-42.
Scharnagl H, März W. New lipid-lowering agents acting on LDL receptors. Curr Top Med Chem. 2005;5(3):233-42.
Scharnagl, H., & März, W. (2005). New lipid-lowering agents acting on LDL receptors. Current Topics in Medicinal Chemistry, 5(3), 233-42.
Scharnagl H, März W. New Lipid-lowering Agents Acting On LDL Receptors. Curr Top Med Chem. 2005;5(3):233-42. PubMed PMID: 15857307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New lipid-lowering agents acting on LDL receptors. AU - Scharnagl,Hubert, AU - März,Winfried, PY - 2005/4/29/pubmed PY - 2005/6/18/medline PY - 2005/4/29/entrez SP - 233 EP - 42 JF - Current topics in medicinal chemistry JO - Curr Top Med Chem VL - 5 IS - 3 N2 - The treatment of dyslipoproteinemia has proven a successful strategy in the prevention of cardiovascular diseases. The major target of hypolipidemic drugs is the reduction of low density lipoprotein cholesterol (LDL-C). HMG-CoA reductase inhibitors (HMGRI) effectively lower LDL-C by inhibiting the mevalonate pathway and enhancing the activity of the LDL receptor (LDL-R). Numerous clinical studies demonstrated convincingly, that the reduction of LDL-C lowers the incidence of cardiovascular events in primary and secondary prevention. Two new HMGRI, rosuvastatin and pitavastatin, have been evaluated in clinical trials. Both drugs demonstrated efficacy in lowering atherogenic lipoproteins. In addition to the reduction of LDL-C, they may have a higher potency to lower triacylglycerides (TG) and to increase HDL cholesterol (HDL-C) compared to currently available HMGRI. Other therapeutic strategies examined in experimental animals are the inhibition of squalene synthase, the first enzyme of the mevalonate pathway, which is specifically committed to cholesterol biosynthesis, and the direct up-regulation of LDL receptor activity. The latter compounds, the SCAP ligands, are the first members of a new class of hypolipidemic agents affecting the transcriptional regulation of genes involved in lipid metabolism. Recent treatment guidelines emphasise the importance of modifying lipid metabolism beyond lowering LDL-C, mainly by lowering TG and raising HDL-C. Although these actions are not primary targets of the compounds discussed here, it is interesting that drugs inducing the LDL-R usually also lower TG and, in the case of HMGRI, increase HDL-C. SN - 1568-0266 UR - https://www.unboundmedicine.com/medline/citation/15857307/New_lipid_lowering_agents_acting_on_LDL_receptors_ L2 - http://www.eurekaselect.com/79176/article DB - PRIME DP - Unbound Medicine ER -