Proprotein convertase subtilisin/kexin type 9 (PCSK9) down-regulates the low-density lipoprotein (LDL) receptor, elevating LDL cholesterol and accelerating atherosclerotic heart disease, making it a promising cardiovascular drug target.
It is an autosomal dominant disease, caused by variants in Ldlr, ApoB or Pcsk9, which results in high levels of LDL-cholesterol (LDL-C) leading to early coronary heart disease.
Consequently, the role of PCSK9 in modulating circulating LDL makes it a promising therapeutic target for treating hypercholesterolemia and coronary heart disease.
Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor.
Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL.Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation.
A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis.
We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus.
Loss-of-function mutations in PCSK9 cause familial hypobetalipoproteinemia, which appears to lower risk for coronary artery disease and has no adverse sequelae.
We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9.
The PCSK9 gene E670G polymorphism affects low-density lipoprotein cholesterol levels but is not a risk factor for coronary artery disease in ethnic Chinese in Taiwan.
The secondary end points are (1) MACE developed from visit 1 to visit 2 (day 30); (2) MACE developed from visit 2 (day 30) to visit 5 (day 730); (3) treatment rate by lipid-lowering therapies (any statin or intensive, PCSK9 inhibitor, fibrates and ezetimibe); (4) incidence of events by the addition of the following outcomes to the primary end point: coronary revascularisation due to myocardial ischaemia, revascularisation other than coronary artery, inpatient treatment for occurrence or exacerbation of heart failure, transient ischaemic attack, acute arterial occlusion, central retinal artery occlusion and other adverse events prolonging or requiring hospitalisation and (5) proportion of subjects achieving target lipid levels.
This review aims to discuss the impact of natural mutations in the PCSK9 gene on cholesterol metabolism and thus coronary artery disease, as well as molecular mechanisms and therapeutic strategies for PCSK9 inhibition.
Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease.
Cost effectiveness of lifelong therapy with PCSK9 inhibitors for lowering cardiovascular events in patients with stable coronary artery disease: Insights from the Ludwigshafen Risk and Cardiovascular Health cohort.
Background Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to be related to several risk factors and diseases such as inflammatory markers and coronary artery disease.
Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.
In statin treated asymptomatic FH patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease.
A state transition Markov model was developed to model the cost-effectiveness of PCSK9 inhibitors for prevention of coronary heart disease, ischaemic strokes, and death among high-risk patient subpopulations in Norway, in both primary and secondary settings.
The GLAGOV trial compared the effect of the PCSK9 inhibitor, evolocumab, and placebo on progression of coronary atherosclerosis in patients treated with at least moderate intensity statin therapy.
We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes.
PCSK9 gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while PCSK9 loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease.