Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Scharnagl, H; März, W.
New lipid-lowering agents acting on LDL receptors.
CURR TOP MED CHEM. 2005; 5(3): 233-242.
Doi: 10.2174/1568026053544524
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Scharnagl Hubert
- Co-authors Med Uni Graz
- März Winfried
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Antilipemic Agents - pharmacology
- Arteriosclerosis - drug therapy
- Cholesterol, LDL - blood
- Farnesyl-Diphosphate Farnesyltransferase - antagonists and inhibitors
- Humans - antagonists and inhibitors
- Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
- Hypercholesterolemia - complications
- Lipid Metabolism - complications
- Lipids - blood
- Mevalonic Acid - metabolism
- Receptors, LDL - blood
- Transcription, Genetic - blood
- Find related publications in this database (Keywords)
- LDL receptor
- HMG-CoA reductase inhibitors
- squalene synthase inhibitors
- SCAP ligands
- coronary artery disease
- LDL cholesterol