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The Promise of PCSK9 and Lipoprotein(a) as Targets for Gene Silencing Therapies
Clin Ther. 2023 Jul 29:S0149-2918(23)00258-8. doi: 10.1016/j.clinthera.2023.07.008. Online ahead of print.ABSTRACTPURPOSE: High plasma concentrations of LDL and lipoprotein(a) (Lp[a]) are independent and causal risk factors for atherosclerotic cardiovascular disease (ASCVD). There is an unmet therapeutic need for high-risk patients with elevated levels of LDL-C and/or Lp(a). Recent advances in the development of nucleic acids for gene silencing (ie, triantennary N-acetylgalactosamine conjugated antisense-oligonucleotides [ASOs] and small interfering RNA [siRNA]) targeting proprotein convertase subtilisin/kexin type 9 (PCSK...
Source: Clinical Therapeutics - July 31, 2023 Category: Drugs & Pharmacology Authors: Dick C Chan Gerald F Watts Source Type: research

Role of Lipoprotein(a) in Atherosclerotic Cardiovascular Disease: A Review of Current and Emerging Therapies
AbstractLipoprotein(a), or Lp(a), is structurally like low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but i...
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - July 19, 2023 Category: Drugs & Pharmacology Authors: Ibrahim S. Alhomoud, Azita Talasaz, Anurag Mehta, Michael Kelly, Evan M. Sisson, John D. Bucheit, Roy Brown, Dave L. Dixon Tags: REVIEW Source Type: research

SIRT6 regulates endothelium-dependent relaxation by modulating nitric oxide synthase 3 (NOS3)
CONCLUSIONS: We identified SIRT6 as a new regulator of the activity of NOS3, with functional implications for endothelial-dependent relaxation.PMID:36720357 | DOI:10.1016/j.bcp.2023.115439
Source: Biochemical Pharmacology - January 31, 2023 Category: Drugs & Pharmacology Authors: Jiaojiao Wang Zhiping Liu Jing Lu Jiami Zou Weile Ye Hong Li Si Gao Peiqing Liu Source Type: research

Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy
In conclusion, the results suggested that GB may improve DN via protecting the kidney from ferroptosis and oxidative stress damage by inhibiting the ubiquitination of GPX4. These findings suggested that GB, a natural medicine, may be an effective therapeutic option for DN.PMID:36411664 | DOI:10.1016/j.biopha.2022.113953
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - November 22, 2022 Category: Drugs & Pharmacology Authors: Jing Chen Zhijie Ou Tiantian Gao Yuwei Yang Anmei Shu Huiqin Xu Yuping Chen Zhiyang Lv Source Type: research

MiR-133a-3p/Sirt1 epigenetic programming mediates hypercholesterolemia susceptibility in female offspring induced by prenatal dexamethasone exposure
In conclusion, PDE can cause persistent enhancement of hepatic cholesterol synthesis function before and after birth through GR/miR-133a-3p/Sirt1 pathway, eventually leading to increased hypercholesterolemia susceptibility in female offspring rats.PMID:36326533 | DOI:10.1016/j.bcp.2022.115306
Source: Biochemical Pharmacology - November 3, 2022 Category: Drugs & Pharmacology Authors: Xufeng Li Wen Hu Li Li Ze Chen Tao Jiang Dingmei Zhang Kexin Liu Hui Wang Source Type: research

Translational Population-Pharmacodynamic Modeling of a Novel Long-Acting siRNA Therapy, Inclisiran, for the Treatment of Hypercholesterolemia
Clin Pharmacol Ther. 2022 Oct 25. doi: 10.1002/cpt.2774. Online ahead of print.ABSTRACTInclisiran is a novel N-acetylgalactosamine (GalNAc) conjugated small-interfering ribonucleic acid (siRNA) therapy designed to specifically target proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA in the liver for the treatment of hypercholesterolemia. Inclisiran's GalNAc attachment results in a rapid uptake into the liver, and thus a short plasma half-life, but long duration of effects on PCSK9 inhibition and low-density lipoprotein cholesterol (LDL-C) lowering. The effects on PCSK9 inhibition and consequent LDL-C reduction are...
Source: Clinical Pharmacology and Therapeutics - October 25, 2022 Category: Drugs & Pharmacology Authors: Nathalie H Gosselin Virna J A Schuck Olivier Barriere Kenneth Kulmatycki Alison Margolskee Patrick Smith YanLing He Source Type: research

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