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10.1016/j.jacc.2013.07.056 http://scihub22266oqcxt.onion/10.1016/j.jacc.2013.07.056 23973703!ä!23973703 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Am+Coll+Cardiol 2013 ; 62 (16): 1401-8 Nephropedia Template TP {{tp|p=23973703|t=2013. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis |pdf=|usr=}}{{23973703}} gab.com Text Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis JO: J Am Coll Cardiol http://www.kidney.de/pget.php?&tw=1&pmid=23973703 #FOAvip Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations are linked to low plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in response to statin treatment activate the sterol regulatory element-binding protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this self-regulatory mechanism contributes to maintain cholesterol homeostasis preventing excessive cholesterol uptake, it may limit the therapeutic effect of statins. A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Moreover, experimental studies indicate that PCSK9 might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDLR. Further research is needed to characterize the potential therapeutic and to rule out unwanted off-target effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and summarize current therapeutic strategies targeting PCSK9. Twit Text FOAVip Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis ????J Am Coll Cardiol http://www.kidney.de/pget.php?&tw=1&pmid=23973703 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23973703 #FOAvip English Wikipedia <ref>{{Cite pmid|23973703}}</ref> Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis #MMPMID23973703 Urban D; Poss J; Bohm M; Laufs U J Am Coll Cardiol 2013[Oct]; 62 (16): 1401-8 PMID23973703show ga Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations are linked to low plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in response to statin treatment activate the sterol regulatory element-binding protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this self-regulatory mechanism contributes to maintain cholesterol homeostasis preventing excessive cholesterol uptake, it may limit the therapeutic effect of statins. A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Moreover, experimental studies indicate that PCSK9 might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDLR. Further research is needed to characterize the potential therapeutic and to rule out unwanted off-target effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and summarize current therapeutic strategies targeting PCSK9. |*Atherosclerosis/complications/drug therapy/metabolism[MESH] |*Dyslipidemias/complications/drug therapy/metabolism[MESH] |*Molecular Targeted Therapy/methods/trends[MESH] |*Proprotein Convertases/antagonists & inhibitors/genetics/metabolism[MESH] |*Serine Endopeptidases/genetics/metabolism[MESH] |Forecasting[MESH] |Humans[MESH] |Hypolipidemic Agents/*pharmacology[MESH] |Lipid Metabolism/drug effects/genetics[MESH] |Lipoproteins, LDL/genetics/metabolism[MESH] |Mutation[MESH] |Proprotein Convertase 9[MESH] |Receptors, LDL/genetics/metabolism[MESH]Targeting the proprotein convertase subtilisin/kexin type 9 for the tr(epmc).pdf DeepDyve Pubget Overpricing