Cardiovascular endocrinology in 2012: PCSK9—an exciting target for reducing LDL-cholesterol levels

  title={Cardiovascular endocrinology in 2012: PCSK9—an exciting target for reducing LDL-cholesterol levels},
  author={D. John Betteridge},
  journal={Nature Reviews Endocrinology},
  • D. J. Betteridge
  • Published 8 January 2013
  • Medicine, Biology
  • Nature Reviews Endocrinology
Systemic administration of anti-PCSK9 antibodies induces dramatic reductions in LDL-cholesterol levels, and the effect of this therapy on LDL-receptor activity seems to be additive to that of statin therapy. Inhibition of PCSK9 is potentially very important to the clinician, and should enable more patients to achieve their LDL-cholesterol-level goal. 
PCSK9 Inhibitors: Research and new perspectives in clinical practice
Safety of new drugs compared to placebo seems acceptable but final conclusions will be drawn when studies are completed.
Update on the Pharmacologic Agents for Dyslipidemia
Although statins have demonstrated consistent and strong effects on cardiovascular prevention, non-statin drugs have failed to show additional clinical benefit, and it is important to have correct knowledge on these agents for optimal treatment of dyslipidemic patients.
CCN family member 1 deregulates cholesterol metabolism and aggravates atherosclerosis
CCN family member 1 (CCN1) is an extracellular matrix cytokine and appears in atherosclerotic lesions. However, we have no evidence to support the role of CCN1 in regulating cholesterol metabolism
Triple Targeting Delivery of CRISRP/Cas9 to Reduce the Risk of Cardiovascular Diseases.
Gal-LGCP successfully targeted to the liver where PCSK9 is specifically expressed and led to effective mutation in Pcsk9 and ~30% of plasma LDL-C decrease in mice, suggesting this approach may have therapeutic potential for the prevention and treatment of cardiovascular disease without side effects.
Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6‐trinitrobenzenesulfonic acid‐induced colitis via repressing toll‐like receptor 4/nuclear factor‐kappa B
PCSK9 inhibition attenuated TNBS‐induced rat colitis through anti‐inflammatory effect under inactivation of TLR4/NF‐κB, suggesting potential therapeutic strategy in IBD.
Synthetic multi-layer nanoparticles for CRISPR-Cas9 genome editing.
Making Sense of Genes
Making Sense of Genes is an accessible but rigorous introduction to contemporary genetics concepts for non-experts, undergraduate students, teachers and healthcare professionals.


Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial.
In this phase 2 study in statin-intolerant patients, subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability.
Effect of a monoclonal antibody to PCSK9 on LDL cholesterol
It is found that REGN727/SAR236553 (REGN727), a human proprotein convertase subtilisin/kexin 9 (PCSK9) monoclonal antibody, lowers levels of low-density lipoprotein (LDL) cholesterol in patients with familial and nonfamilial hypercholesterolemia.
Effect of a monoclonal antibody to PCSK9 on LDL cholesterol.
In three phase 1 trials, a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels in healthy volunteers and in subjects with familial or nonfamilial hypercholesterolemia.
The PCSK9 decade
Initial data from investigations of PCSK9 inhibition in humans are promising and indicate that PCSK 9 inhibition may be a viable new therapeutic option for the treatment of dyslipidemia and associated cardiovascular diseases.
Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
Two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH are reported, a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.