ライフサイエンスコーパス: PCSK9

1 oprotein convertase subtilisin-kexin type 9 (PCSK9).

2 oprotein convertase subtilisin/kexin type 9 (PCSK9).

3 (3) ELISA quantification of Lp(a)-associated PCSK9.

4 uency missense variants in the genes LPA and PCSK9.

5 asma levels of approximately 300 ng/ml human PCSK9.

6 emia and a 7- to 24-fold induction in plasma PCSK9.

7 ognize the C-terminal Cys-His-rich domain of PCSK9.

8 on of SREBP2 and subsequent transcription of PCSK9.

9 ), was lost in mice with hepatic deletion of Pcsk9 (5% in both the presence and absence of NTS).

10 oprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that degrades low-density

11 oprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipopro

12 scribed that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small

13 lesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in

14 l-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR.

15 argets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of t

16 Inhibition of PCSK9 also results in reductions of plasma lipoprotein (

17 ally, we found that for missense SNPs within PCSK9, alterations in both proteolysis and secretion are

18 inductions in plasma PCSK9, and knockout of Pcsk9 ameliorates dyslipidemia in a mouse model of nephr

19 confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR.

20 cholesterol, 1.11 (95% CI, 1.04 to 1.19) for PCSK9 and 1.13 (95% CI, 1.06 to 1.20) for HMGCR.

21 The direct correlation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism poten

22 eated with antiplatelet therapy, circulating PCSK9 and 11-dh-TxB2 were significantly correlated (Spea

23 tly inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl-coenzyme A reductas

24 ied two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci.

25 The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC s

26 s study investigated the association between PCSK9 and CVEs in AF as well as the relationship between

27 When present together, PCSK9 and HMGCR variants had additive effects on the ris

28 Variants in PCSK9 and HMGCR were associated with nearly identical pr

29 oprecipitation of plasma using antibodies to PCSK9 and immunodetection of apo(a); (3) ELISA quantific

30 The relationship between circulating PCSK9 and incident CVD in the general population is unkn

31 tiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months.

32 In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high

33 At day 240, PCSK9 and LDL cholesterol levels remained significantly

34 inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels.

35 Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for

36 Including PCSK9 and LDLR improved risk score performance.

37 Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and

38 ermine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previo

39 Characterize the association of PCSK9 and Lp(a) in 39 subjects with high Lp(a) levels (r

40 PCSK9 and plasma lipids were studied in nephrotic syndro

41 further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following ora

42 companied by significant reductions in serum Pcsk9 and total cholesterol levels.

43 Es in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2)

44 At admission, plasma PCSK9 and urinary 11-dh-TxB2 (n = 852) were measured.

45 Pcsk9 deficient (pcsk9 (-/-)) and wild-type (WT) littermates underwent pa

46 oprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) choleste

47 oprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LD

48 oprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1).

49 damage triggers marked inductions in plasma PCSK9, and knockout of Pcsk9 ameliorates dyslipidemia in

50 evidence highlights a potential key role of PCSK9 antibodies in managing acute coronary syndrome.

51 The authors posit a rationale for the use of PCSK9 antibodies in patients with acute coronary syndrom

52 Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density

53 This review describes the influence of PCSK9 antibodies on plaque composition and instability,

54 Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,0

55 Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with F

56 The induction of plasma PCSK9 appeared to be attributable to increased secretion

57 oprotein convertase subtilisin/kexin type 9 (PCSK9) are an emerging therapy for dyslipidemia.

58 oprotein convertase subtilisin-kexin type 9 (PCSK9) are being evaluated in clinical trials for the tr

59 In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated b

60 lation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism potentially implicated in platelet

61 several additional approaches to inhibiting PCSK9, as well as other classes of LDL-lowering therapie

62 orvastatin lowered the concentration of free PCSK9, atorvastatin lowered the lathosterol/campesterol

63 oprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), pr

64 not required for the degradation of CD81 by PCSK9, but its presence strengthened the PCSK9 effect.

65 No mutations were found in either APOB or PCSK9, but nine probands were homozygous for seven diffe

66 compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34,

67 to interrogate the sequence specificities of PCSK9 cleavage and proteolysis-independent secretion.

68 Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,0

69 Serum PCSK9 concentration is associated with future risk of CV

70 We investigated whether serum PCSK9 concentration is associated with incident CVD in a

71 Baseline serum PCSK9 concentration predicted incident CVD; concentratio

72 regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low de

73 ies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC.

74 Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for PCSK9 p

75 oprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice.

76 Pcsk9 deficient (pcsk9 (-/-)) and wild-type (WT) litterm

77 PCSK9 did not bind to apo(a) only, and the association o

78 oprotein convertase subtilisin/kexin type 9 (PCSK9) down-regulates the low-density lipoprotein (LDL)

79 of AUD showed that alcohol exposure leads to PCSK9 downregulation.

80 by PCSK9, but its presence strengthened the PCSK9 effect.

81 e of two independent effects of ER stress on PCSK9 expression and secretion.

82 functional involvement in the suppression of PCSK9 expression by berberine (BBR), a natural cholester

83 JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells.

84 abolism by examining its ability to modulate PCSK9 expression.

85 n, induced SREBP2-dependent up-regulation of PCSK9 expression.

86 he first evidence that GPC3 can modulate the PCSK9 extracellular activity as a competitive binding pa

87 The population was divided into tertiles of PCSK9 for the analysis.

88 to be attributable to increased secretion of PCSK9 from the hepatocyte coupled with decreased clearan

89 F1alpha) as an obligated trans-activator for PCSK9 gene expression and demonstrated its functional in

90 he proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes.

91 Mutations in the LDLR, APOB, and PCSK9 genes are known to cause FH.

92 creened for mutations in the LDLR, APOB, and PCSK9 genes using next generation sequencing, with resul

93 Therefore, we hypothesized that certain PCSK9 genetic variants may modify the association betwee

94 enetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blo

95 For PCSK9 genetic variants, the OR for type 2 diabetes per 1

96 regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by

97 PCSK9 GOF mutation carriers have elevated LDL-C levels a

98 eeks to 13 patients representing 4 different PCSK9 GOF mutations with low-density lipoprotein cholest

99 In this study, variants in PCSK9 had approximately the same effect as variants in H

100 cular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or

101 oprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed to treat hyperlipidemia.

102 oprotein convertase subtilisin/kexin type 9 (PCSK9) has been extensively studied; however, many steps

103 oprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular

104 d that the third versus the first tertile of PCSK9 (hazard ratio: 1.640; 95% confidence interval: 1.1

105 r of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1.

106 rol levels that were mediated by variants in PCSK9, HMGCR, or both on the risk of cardiovascular even

107 Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of

108 TNF-alpha induced both SOCS3 and PCSK9 in a concentration-dependent manner.

109 diovascular Outcomes Following Inhibition of PCSK9 in Different Populations.

110 there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value

111 Here, we tested the role of PCSK9 in mediating the hypercholesterolemia of nephrotic

112 udies provide evidence that the retention of PCSK9 in the ER may serve as a potential strategy for lo

113 injection into mice induces >80% editing of Pcsk9 in the liver.

114 d Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events),

115 urther Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER

116 urther Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER

117 urther Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial a

118 urther Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).

119 studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes.

120 nd antithrombotic mechanisms associated with PCSK9 inhibition that may confer benefits during the ear

121 Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.

122 Objective: To determine the effects of PCSK9 inhibition with evolocumab on progression of coron

123 INTERPRETATION: PCSK9 inhibition with evolocumab significantly reduced c

124 e at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced t

125 lable to clear IDL and LDL from blood during PCSK9 inhibition.

126 In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab ha

127 The model incorporated 2015 annual PCSK9 inhibitor costs of $14,350 (based on mean wholesal

128 In trials of PCSK9 inhibitor drugs, investigators should carefully as

129 We compared the effect of the PCSK9 inhibitor evolocumab on lipid parameters in patien

130 In the longest clinical trial exposure to a PCSK9 inhibitor to date, evolocumab produced sustained r

131 comes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for st

132 At 2015 prices, PCSK9 inhibitor use in all eligible patients was estimat

133 Assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous FH or

134 e of patients with ASCVD who would require a PCSK9 inhibitor when oral lipid-lowering therapy (LLT) i

135 therapy; add-on alirocumab therapy, 75 mg (a PCSK9 inhibitor); and uptitration to alirocumab, 150 mg.

136 s, with only a modest percentage requiring a PCSK9 inhibitor.

137 statins plus ezetimibe, and 14% with add-on PCSK9 inhibitor.

138 ensitivity analyses included evolocumab as a PCSK9 inhibitor.

139 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in a subset of patients with

140 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduced LDL cholesterol and

141 Although PCSK9 inhibitors (PCSK9i) were approved in 2015, their h

142 Our analysis suggests that PCSK9 inhibitors are not associated with an increased ri

143 The projected cost effectiveness of PCSK9 inhibitors does not meet generally accepted benchm

144 on making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or

145 algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL

146 The list prices of PCSK9 inhibitors in the United States (>$14,500 per year

147 These data suggest that PCSK9 inhibitors may be beneficial in patients with neph

148 al patients, the high out-of-pocket costs of PCSK9 inhibitors may impede access and reduce long-term

149 ed biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.

150 human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.

151 , was used to evaluate cost-effectiveness of PCSK9 inhibitors or ezetimibe in heterozygous FH or ASCV

152 safety data are still needed, antibody-based PCSK9 inhibitors promise to meet much of the unmet medic

153 4536 per patient or less would be needed for PCSK9 inhibitors to be cost-effective at less than $100,

154 Adding PCSK9 inhibitors to statins in heterozygous FH was estim

155 In ASCVD, adding PCSK9 inhibitors to statins was estimated to prevent 4.3

156 rom ongoing cardiovascular outcome trials of PCSK9 inhibitors will provide additional data to inform

157 The budgetary impact of PCSK9 inhibitors would be very large if all potentially

158 ive cholesterol-lowering treatment (eg, with PCSK9 inhibitors).

159 usses the history and mechanism of action of PCSK9 inhibitors, their metabolic effects, and clinical

160 L receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies chara

161 studies to evaluate the long-term safety of PCSK9 inhibitors.

162 OR, 1.44; 95% CI, 0.57-3.65) with the use of PCSK9 inhibitors.

163 w hope for the development of small-molecule PCSK9 inhibitors.

164 ive therapies, including new agents, such as PCSK9 inhibitors.

165 erapy compared with addition of ezetimibe or PCSK9 inhibitors.

166 OR, 2.85; 95% CI, 1.34-6.06) with the use of PCSK9 inhibitors.

167 oprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs o

168 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with persistently elevated

169 of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD.

170 oprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in

171 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors substantially reduce low-density lipop

172 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering lo

173 oprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors, are discussed.

174 oprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remai

175 t an unbiased screening approach to identify PCSK9-interacting proteins in the HepG2 cells' secretome

176 PCSK9 is a risk predictor and a biotarget in atheroscler

177 In conclusion, deficiency of PCSK9 is associated with protection from venous thrombos

178 esults show, for the first time, that plasma PCSK9 is found in association with Lp(a) particles in hu

179 We show that PCSK9 is physically associated with Lp(a) in vivo using

180 PCSK9 is primarily expressed in the liver and regulates

181 Serum Pcsk9 is reduced to undetectable levels, and cholesterol

182 oprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low

183 Pcsk9 knock-out mice expressing a human bacterial artifi

184 Recent studies have shown that PCSK9 lacking its Cys/His-rich domain can still promote

185 ls as a consequence of the disruption of the PCSK9/LDL receptor regulatory axis.

186 m of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with hear

187 The PCSK9-LDLR axis was associated with outcomes in patients

188 he Cys-His-rich domain-dependent sorting the PCSK9-LDLR complex to lysosomes.

189 clisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.

190 mab varies based on an individual's baseline PCSK9 level remains unknown.

191 The median baseline circulating PCSK9 level was 323 ng/mL (interquartile range, 258-406

192 ffect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipi

193 etween 64% and 71% (P < .001), regardless of PCSK9 levels (P for interaction = .76 and .21, respectiv

194 large cardiovascular outcomes trial suppress PCSK9 levels and consistently and substantially reduce L

195 esults suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of

196 To characterize variability in PCSK9 levels and determine whether the LDL-C level reduc

197 statin use, there was no correlation between PCSK9 levels and LDL-C levels (rho = 0.03 [95% CI, -0.04

198 vealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR

199 Plasma PCSK9 levels are associated with an increased risk of CV

200 d 420 mg once monthly suppressed circulating PCSK9 levels by 90% to 100% within 1 week of administrat

201 Plasma PCSK9 levels correlated with Lp(a) levels, but not with

202 Finally, Lp(a)-associated PCSK9 levels directly correlated with plasma Lp(a) level

203 No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) a

204 coronary events induce a dynamic increase of PCSK9 levels that may play a role in plaque vulnerabilit

205 Mean baseline PCSK9 levels were higher with high versus moderate and l

206 substudy from 4 phase 2 trials, circulating PCSK9 levels were measured at baseline and then weekly a

207 Circulating PCSK9 levels were measured at baseline using quantitativ

208 d by background statin dose due to increased PCSK9 levels with higher statin doses.

209 Across all quartiles of baseline PCSK9 levels, both evolocumab 140 mg every 2 weeks and 4

210 Regardless of baseline PCSK9 levels, the doses of evolocumab being studied in a

211 on achieved with evolocumab differs based on PCSK9 levels.

212 lasma Lp(a) levels but not with total plasma PCSK9 levels.

213 g once monthly, across quartiles of baseline PCSK9 levels.

214 oprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively corr

215 oprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240.

216 imilar between participants with and without PCSK9 LOF variants (all P>0.10).

217 djusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (

218 We investigated the association between PCSK9 LOF variants and neurocognitive impairment and dec

219 airment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [C

220 ed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% co

221 PCSK9 LOF variants were associated with a pooled odds ra

222 PCSK9 LOF variants were associated with lower LDL-C and

223 PCSK9 LOF variants were not associated with incident str

224 PCSK9 LOF variants were not associated with stroke risk.

225 We examined the association of PCSK9 LOF variants with LDL-C and incident coronary hear

226 0.05) among participants with versus without PCSK9 LOF variants.

227 PCSK9 loss-of-function (LOF) variants allow for the exam

228 PCSK9 loss-of-function (LOF) variants that result in lif

229 In vivo PCSK9 lowering by oral dosing of the candidate prodrug a

230 oprotein convertase subtilisin/kexin type 9 (PCSK9), lowering LDL by about 50-60%.

231 oprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) chol

232 isin/kexin type 9) as an alternative to anti-PCSK9 mAbs.

233 Lp(a)-bound PCSK9 may be pursued as a biomarker for cardiovascular r

234 9, the LDLR-R410S was resistant to exogenous PCSK9-mediated degradation in endosomes/lysosomes and sh

235 +) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-depen

236 that the selected sdAbs efficiently blocked PCSK9-mediated low density lipoprotein receptor (LDLR) d

237 zed small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained redu

238 sis was evident in 60% of WT mice and 25% of pcsk9 (-/-) mice (p < 0.05).

239 however leukocyte attachment was reduced in pcsk9 (-/-) mice compared to WT mice.

240 ular trap formation (NETs) in WT compared to pcsk9 (-/-) mice.

241 PCSK9 monoclonal antibodies have been shown to reduce LD

242 for understanding the potential benefits of PCSK9 monoclonal antibodies incremental to statins in on

243 The mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism re

244 Adding ezetimibe or PCSK9 monoclonal antibodies to maximally tolerated stati

245 tein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by

246 zetimibe therapy, even in combination with a PCSK9 monoclonal antibody injection.

247 Adding a PCSK9 monoclonal antibody to lower LDL-C by at least 50%

248 inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter a

249 Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observ

250 a decrease in plasma cholesterol and plasma PCSK9 on remission of their disease (P<0.05, n=47-50).

251 otein (LDL) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes i

252 9 deficiency (each compound heterozygote for PCSK9 p.Y142X and p.C679X) were identified, with one hav

253 oprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plas

254 Biological validation showed that PCSK9 promoter methylation is conserved across tissues a

255 ere the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as

256 PCSK9 (proprotein convertase subtilisin/kexin type 9) ha

257 The PCSK9 (proprotein convertase subtilisin/kexin type 9) in

258 ocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), m

259 ents raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) in

260 ignificant reduction in the secreted form of PCSK9 protein was observed in the media from both thapsi

261 Our findings indicate that PCSK9 proteolysis acts as a commonly perturbed but criti

262 rase readout to evaluate the single-turnover PCSK9 proteolytic event.

263 These data confirm that PCSK9 reduces CD81 levels via an intracellular pathway a

264 oprotein convertase subtilisin-kexin type 9 (PCSK9), reduces levels of low-density lipoprotein (LDL)

265 of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms betwee

266 ieve its maximal effect on the LDL receptor, PCSK9 requires autoproteolysis.

267 in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009).

268 After cleavage, PCSK9 retains its prodomain in the active site as a self

269 risk of nonfatal MI in C-allele carriers of PCSK9 rs11206510 (n = 799) but not in non-C-allele carri

270 served a significant interaction between the PCSK9 rs11206510 genotype and LC n-3 PUFA intake on nonf

271 d a complete biochemical characterization of PCSK9's proteolytic function, which could inform therape

272 show that some SNPs allosterically modulate PCSK9's substrate sequence specificity.

273 eir ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR de

274 oprotein convertase subtilisin/kexin type 9 (PCSK9) selectively binds low-density lipoprotein; we hyp

275 ment known structural data, and suggest that PCSK9 self-proteolysis is the rate-limiting step of secr

276 in the presence of NTS, mice lacking hepatic Pcsk9 showed a 40% to 50% decrease in plasma cholesterol

277 with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA.

278 sterol and coronary artery disease risk gene PCSK9 STARNET provides insights into gene-regulatory mec

279 oprotein convertase subtilisin kexin type 9 (PCSK9), such as evolocumab, lower plasma low-density lip

280 f-principle for the future usage of sdAbs as PCSK9-targeting drugs that can efficiently reduce LDL-ch

281 s a fully human, monoclonal antibody against PCSK9 that reduces low-density lipoprotein cholesterol (

282 d bound equally well to LDL or extracellular PCSK9, the LDLR-R410S was resistant to exogenous PCSK9-m

283 ed with NTS to determine the contribution of PCSK9 to the dyslipidemia of nephrotic syndrome.

284 d that the sdAb-Fcs do not affect binding of PCSK9 to the LDLR but rather block its induced cellular

285 46 is highly selective for the inhibition of PCSK9 translation.

286 multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% fro

287 intake and CVD risk.We determined whether a PCSK9 variant (rs11206510), which has been identified fo

288 Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and r

289 PCSK9 variants associated with lower LDL cholesterol wer

290 INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol wer

291 the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarke

292 oprotein convertase subtilisin kexin type 9 (PCSK9) vary markedly across the population and are influ

293 oprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to have a mutually regulating relation

294 After immunizing a llama with human PCSK9, we selected four sdAbs that bind PCSK9 with a hig

295 Null and damaging missense variants in PCSK9 were associated with 36 mg/dL lower low-density li

296 Patients with higher levels of PCSK9 were more likely to be receiving intensive statin

297 In addition, mice with hepatic deletion of Pcsk9 were treated with NTS to determine the contributio

298 uman PCSK9, we selected four sdAbs that bind PCSK9 with a high affinity and produced them as fusion p

299 In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy

300 Preferential association of PCSK9 with Lp(a) versus low-density lipoprotein (1.7-fol

301 bind to apo(a) only, and the association of PCSK9 with Lp(a) was not affected by the loss of the apo