Sandbox 215: Difference between revisions
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[http://en.wikipedia.org/wiki/LDL LDL particles] are constitued of a single apolipoprotein which is apo-B100. They are often called “bad cholesterol” because a high rate of LDL leads to a deposition of cholesterol as plaques on artery walls and that can causes cardiovascular problems. | [http://en.wikipedia.org/wiki/LDL LDL particles] are constitued of a single apolipoprotein which is apo-B100. They are often called “bad cholesterol” because a high rate of LDL leads to a deposition of cholesterol as plaques on artery walls and that can causes cardiovascular problems. | ||
Unlike to LDL,[http://en.wikipedia.org/wiki/High-density_lipoprotein HDL particles] are considered as “good cholesterol” because they are able to remove cholesterol, via the plasma, from peripheral tissues to the liver, where it will be degraded. They are constitued of apolipoproteins A-I and apo A-II. In fact, a high level of HDL can prevent from the accumulation of cholesterol in the plasma and avoid the developpement of cardiovascular diseases and atherosclerosis. That's why a promising solution to increase the level of HDL is the inhition of CETP. <ref>James A Hamilton & Richard J Deckelbaum. Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? Nature Structural & Molecular Biology 14, 95 - 97 (2007). [https://www-ncbi-nlm-nih-gov.scd-rproxy.u-strasbg.fr/pubmed/17277799 PMID: 17277799] [http://www.nature.com.scd-rproxy.u-strasbg.fr/nsmb/journal/v14/n2/full/nsmb0207-95.html doi:10.1038/nsmb0207-95]</ref> | Unlike to LDL, [http://en.wikipedia.org/wiki/High-density_lipoprotein HDL particles] are considered as “good cholesterol” because they are able to remove cholesterol, via the plasma, from peripheral tissues to the liver, where it will be degraded. They are constitued of apolipoproteins A-I and apo A-II. In fact, a high level of HDL can prevent from the accumulation of cholesterol in the plasma and avoid the developpement of cardiovascular diseases and atherosclerosis. That's why a promising solution to increase the level of HDL is the inhition of CETP. <ref>James A Hamilton & Richard J Deckelbaum. Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? Nature Structural & Molecular Biology 14, 95 - 97 (2007). [https://www-ncbi-nlm-nih-gov.scd-rproxy.u-strasbg.fr/pubmed/17277799 PMID: 17277799] [http://www.nature.com.scd-rproxy.u-strasbg.fr/nsmb/journal/v14/n2/full/nsmb0207-95.html doi:10.1038/nsmb0207-95]</ref> | ||
===Natural inhibitors=== | ===Natural inhibitors=== | ||
In the human plasma some natural inhibitors of CETP can be found: like Apo-CI, which his main role is to inhibit CETP, probably by altering the elecric charge of HDL. <ref>Philip J. Barter, H. Bryan Brewer, Jr, M. John Chapman, Charles H. Hennekens, Daniel J. Rader and Alan R. Tall. Cholesteryl Ester Transfer Protein : A Novel Target for Raising HDL and Inhibiting Atherosclerosis. Arterioscler Thromb Vasc Biol 2003, 23:160-167: originally published online January 2, 2003.[http://atvb.ahajournals.org/content/23/2/160.full doi: 10.1161/01.ATV.0000054658.91146.64].</ref> | In the human plasma some natural inhibitors of CETP can be found: like Apo-CI, which his main role is to inhibit CETP, probably by altering the elecric charge of HDL. <ref>Philip J. Barter, H. Bryan Brewer, Jr, M. John Chapman, Charles H. Hennekens, Daniel J. Rader and Alan R. Tall. Cholesteryl Ester Transfer Protein : A Novel Target for Raising HDL and Inhibiting Atherosclerosis. Arterioscler Thromb Vasc Biol 2003, 23:160-167: originally published online January 2, 2003.[http://atvb.ahajournals.org/content/23/2/160.full doi: 10.1161/01.ATV.0000054658.91146.64].</ref> | ||
===Pharmaceutical inhibitors=== | ===Pharmaceutical inhibitors=== | ||
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Torcetrapib succeeds in increasing the level of HDL, but his action has some side effects such as increasingthe blood pressure and the concentration of sodium, bicarbonate and aldosterone. That causes the death of many persons at the stage-III of the clinical trial. That's why this inhibitor was abort. | Torcetrapib succeeds in increasing the level of HDL, but his action has some side effects such as increasingthe blood pressure and the concentration of sodium, bicarbonate and aldosterone. That causes the death of many persons at the stage-III of the clinical trial. That's why this inhibitor was abort. | ||
Unlike to torcetrapib, the other do not present any side effect, but they still are in clinical trial. Evacetrapib seems to give the more promising results. <ref>Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. The Journal of Lipid Research, December 2011. [https://www-ncbi-nlm-nih-gov.scd-rproxy.u-strasbg.fr/pubmed/21957197 PMID: 21957197]. [http://www.jlr.org.scd-rproxy.u-strasbg.fr/content/52/12/2169.long doi: 10.1194/jlr.M018069]</ref> | Unlike to torcetrapib, the other do not present any side effect, but they still are in clinical trial. Evacetrapib seems to give the more promising results. <ref>Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. The Journal of Lipid Research, December 2011. [https://www-ncbi-nlm-nih-gov.scd-rproxy.u-strasbg.fr/pubmed/21957197 PMID: 21957197]. [http://www.jlr.org.scd-rproxy.u-strasbg.fr/content/52/12/2169.long doi: 10.1194/jlr.M018069]</ref> | ||
==External ressources== | ==External ressources== | ||
