PCSK9: from biology to clinical applications

Blanchard, Valentin; Khantalin, Ilya; Ramin‐Mangata, Stéphane; Chemello, Kévin; Nativel, Brice; Lambert, Gilles

doi:10.1016/j.pathol.2018.10.012

Cited by 34 publications

(21 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in the maintenance of cholesterol balance [118]. Gain-of-function mutations in this gene are associated with an increase in low-density lipoprotein cholesterol levels (i.e., autosomal dominant hypercholesterolemia), a known risk factor for coronary heart disease [119].…”

Section: Bnancmentioning

confidence: 99%

Bridged Nucleic Acids Reloaded

2019

View full text Add to dashboard Cite

Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs that, when part of these oligomers, enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs is the first-generation bridged nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second-generation BNA, BNANC (2′-O,4′-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but, in some cases, also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds have been researched, the promising results warrant more effort in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future, offering great hope to oligonucleotide-based fields of research and applications.

show abstract

Section: Bnancmentioning

confidence: 99%

Bridged Nucleic Acids Reloaded

2019

View full text Add to dashboard Cite

show abstract

“…Background. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease of the subtilase family [44,45], secreted primarily by the liver [44][45][46] and containing 692 amino acids [46]. PCSK9 is an enzyme accepted as a new biomarker for the lipid metabolism, a novel therapeutic target for hypercholesterolemia, because the inhibition of PCSK9 may be one of the options for lowering cardiovascular risk [47][48][49].…”

Section: Proprotein Convertase Subtilisin/kexin Type 9 (Pcsk9)mentioning

confidence: 99%

“…PCSK9 determines the degradation of LDLR [50] and inhibits receptor recycling in the hepatocyte membrane [6]. The human PCSK9 protein (hPCSK9) is synthesized mainly in the liver, the kidney, the small intestine [46], and the brain [44,45] via sterol regulatory element-binding protein 2 (SREBP-2) regulation [46]. Sterol regulatory element-binding proteins (SREBPs) coordinate the synthesis and cellular uptake for cholesterol and fatty acids [51].…”

Section: Proprotein Convertase Subtilisin/kexin Type 9 (Pcsk9)mentioning

confidence: 99%

Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease

Vlad

Foia

Popescu

et al. 2019

Journal of Diabetes Research

View full text Add to dashboard Cite

Purpose. Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients. Methods. We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD. Results. 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients. Conclusions. Although the “dyslipidemic status” in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.

show abstract

“…PCSK9 encodes neural apoptosis regulated convertase (NARC-1), a human subtilase that is expressed in high amounts in the liver and contributes to cholesterol metabolism. The product of the PCSK9 gene is involved in the breakdown of LDL receptors prior to incorporation in the cell membranes of liver cells (Melendez et al, 2017;Blanchard et al, 2019).…”

Section: The Role Of Pcsk9 In Cholesterol Metabolismmentioning

confidence: 99%

A short review of proprotein convertase subtilisin/kexin type 9 inhibitors

Rudaynah

2019

Reviews in Cardiovascular Medicine

View full text Add to dashboard Cite

Cardiovascular disease is the leading cause of morbidity and mortality globally, as estimated by the World Health Organization, where in 2016, 15.2 million deaths were attributed to ischemic heart disease and stroke. It is therefore essential to try to reduce the incidence of Cardiovascular disease by controlling modifiable risk factors. One such major modifiable risk factor is cholesterol, which influences the pathogenesis and progression of atherosclerosis. Statins are often prescribed to lower blood levels of low density lipoprotein cholesterol, thereby reducing the risk of Cardiovascular disease by approximately 25-35%. However, there is an increasing number of patients (in particular those with intolerance to statin therapy and those with familial hypercholesterolemia) for whom statin therapy alone is not enough to control low density lipoprotein cholesterol. In this review, the regulation of cholesterol metabolism will be discussed with an emphasis on novel cholesterol lowering drugs used in clinical trials. These second-generation drugs, monoclonal antibodies against the low density lipoprotein receptor gene known as proprotein convertase subtilisin/kexin type 9 inhibitors, are expected to be prescribed to patients who are intolerant to statins, as well as in conjunction with statins. Future perspectives of the clinical use of these drugs is also discussed.

show abstract

PCSK9: from biology to clinical applications

Cited by 34 publications

References 77 publications

Bridged Nucleic Acids Reloaded

Bridged Nucleic Acids Reloaded

Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease

A short review of proprotein convertase subtilisin/kexin type 9 inhibitors

Contact Info

Product

Resources

About