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Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.
Graham MJ, Lee RG, Brandt TA, Tai LJ, Fu W, Peralta R, Yu R, Hurh E, Paz E, McEvoy BW, Baker BF, Pham NC, Digenio A, Hughes SG, Geary RS, Witztum JL, Crooke RM, Tsimikas S. Graham MJ, et al. N Engl J Med. 2017 Jul 20;377(3):222-232. doi: 10.1056/NEJMoa1701329. Epub 2017 May 24. N Engl J Med. 2017. PMID: 28538111 Free article. Clinical Trial.
METHODS: We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. ...There were no se …
METHODS: We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on pl …
Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: New therapeutic approaches for the treatment of atherogenic dyslipidemia.
Ruscica M, Zimetti F, Adorni MP, Sirtori CR, Lupo MG, Ferri N. Ruscica M, et al. Pharmacol Res. 2020 Mar;153:104653. doi: 10.1016/j.phrs.2020.104653. Epub 2020 Jan 10. Pharmacol Res. 2020. PMID: 31931117 Review.
Carriers of loss-of-function mutations of ANGPTL4 show instead lower TG-rich lipoproteins and a modest but significant increase of HDL. The relevance of ANGPTL3 and ANGPTL4 as new therapeutic targets is proven by the development of monoclonal antibodies or antisense
Carriers of loss-of-function mutations of ANGPTL4 show instead lower TG-rich lipoproteins and a modest but significant increase of HDL. The …
Lipid lowering therapy in cardiovascular disease: From myth to molecular reality.
Mourikis P, Zako S, Dannenberg L, Nia AM, Heinen Y, Busch L, Richter H, Hohlfeld T, Zeus T, Kelm M, Polzin A. Mourikis P, et al. Pharmacol Ther. 2020 Sep;213:107592. doi: 10.1016/j.pharmthera.2020.107592. Epub 2020 May 31. Pharmacol Ther. 2020. PMID: 32492513 Review.
Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering. At least, using antisense-oligonucleotides against ApoC-III and Lp(a) resulted in promising outcomes. . …
Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effe
Therapeutic oligonucleotides in cardiovascular and metabolic diseases: insights for the internist.
Girelli D, Busti F, Marchi G, Martinelli N, Olivieri O. Girelli D, et al. Intern Emerg Med. 2018 Apr;13(3):313-318. doi: 10.1007/s11739-018-1810-5. Epub 2018 Mar 1. Intern Emerg Med. 2018. PMID: 29498010
Indeed, subjects with null mutations in certain genes controlling lipoprotein metabolism like PCSK9 or ANGPTL-3 have a lower risk of cardiovascular disease. Since the complete absence of such proteins does not appear to carry any negative health effect, the c …
Indeed, subjects with null mutations in certain genes controlling lipoprotein metabolism like PCSK9 or ANGPTL-3 have a lower risk of …
Advances in lipid-lowering therapy through gene-silencing technologies.
Nordestgaard BG, Nicholls SJ, Langsted A, Ray KK, Tybjærg-Hansen A. Nordestgaard BG, et al. Nat Rev Cardiol. 2018 May;15(5):261-272. doi: 10.1038/nrcardio.2018.3. Epub 2018 Feb 8. Nat Rev Cardiol. 2018. PMID: 29417937 Review.
The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse …
The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet count …
ANGPTL3 Inhibitors - Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism.
Geladari E, Tsamadia P, Vallianou NG. Geladari E, et al. Circ J. 2019 Jan 25;83(2):267-273. doi: 10.1253/circj.CJ-18-0442. Epub 2018 Nov 30. Circ J. 2019. PMID: 30504621 Free article. Review.
Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. ...Thus, ongoing …
Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) …
RNA-targeted therapeutics for lipid disorders.
Tsimikas S. Tsimikas S. Curr Opin Lipidol. 2018 Dec;29(6):459-466. doi: 10.1097/MOL.0000000000000549. Curr Opin Lipidol. 2018. PMID: 30234555 Review.
Small inhibiting RNA (siRNA) molecules targeting proprotein convertase subtilisin kexin type 9 to reduce LDL-C, and antisense oligonucleotides (ASO) targeting apolipoprotein C-III (apoC-III) to reduce triglycerides, angiopoietin-like 3 (ANGPTL3) to reduce LDL …
Small inhibiting RNA (siRNA) molecules targeting proprotein convertase subtilisin kexin type 9 to reduce LDL-C, and antisense olig
Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits.
Cho KI, Sakuma I, Sohn IS, Hayashi T, Shimada K, Koh KK. Cho KI, et al. Circ J. 2018 Mar 23;82(4):937-943. doi: 10.1253/circj.CJ-17-1445. Epub 2018 Mar 2. Circ J. 2018. PMID: 29503409 Free article. Review.
However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized this was caused by to off-target effects, but recent studies demonstrate it is caused by on-target effects. ...Patients who ha …
However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized …
Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data.
Strilchuk L, Fogacci F, Cicero AF. Strilchuk L, et al. Expert Opin Drug Saf. 2019 Jul;18(7):611-621. doi: 10.1080/14740338.2019.1620730. Epub 2019 May 29. Expert Opin Drug Saf. 2019. PMID: 31100030 Review.
INTRODUCTION: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. ...After an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocu …
INTRODUCTION: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. ...After an atte …
A new dawn for managing dyslipidemias: The era of rna-based therapies.
Macchi C, Sirtori CR, Corsini A, Santos RD, Watts GF, Ruscica M. Macchi C, et al. Pharmacol Res. 2019 Dec;150:104413. doi: 10.1016/j.phrs.2019.104413. Epub 2019 Aug 23. Pharmacol Res. 2019. PMID: 31449975 Review.
The high occurrence of atherosclerotic cardiovascular disease (ASCVD) events is still a major public health issue. ...In the era of Genome Wide Association Studies and Mendelian Randomization analyses aimed at increasing the understanding of the pathophysiology of ASCVD, R …
The high occurrence of atherosclerotic cardiovascular disease (ASCVD) events is still a major public health issue. ...In the era of G …
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