anti-Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) Antibodies

Human Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) interaction partners

1. Variants at the PCSK9 gene locus seem to be the major genetic determinants of plasma PCSK9 levels.

2. Elevated serum level of PCSK9 can be observed in systemic lupus erythematosus patients, especially in those with thickening of carotid intima-media.

3. Identification and in vitro characterization of two new PCSK9 Gain of Function variants found in patients with Familial Hypercholesterolemia.

4. Demonstration of an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNbeta enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors.

5. In this study, the appropriate virus-like particle (VLP)-peptide vaccines targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) were screened. The screening criteria of target peptides were as follows: located in catalytic domain of PCSK9, or regulating the binding of PCSK9 and LDL receptors (LDLR)

6. This finding is associated with a profound FH phenotype and the highest known plasma PCSK9 level reported in a human. This finding also has therapeutic relevance, as elevated PCSK9 levels may limit the efficacy of high-dose statin therapy and also PCSK9 inhibition

7. PCSK9-mAbs could significantly reduce circulating Lp(a) levels.

8. We conclude that the PCSK9 R496W (rs374603772) and D374Y (rs137852912) GOF mutations may be significant risk factors in the development of primary dyslipidemia and may have significant impact on lipid parameters in general population.

9. High PCSK9 expression is associated with hypothyroidism.

10. This is the first study from a Turkish FH cohort, revealing a higher frequency (approximately 14%) of two PCSK9 GOF mutations (D374Y and R496W)

11. PCSK9 loss-of-function variants were not associated with neurocognitive impairment among a general population sample of middle-age and older African Americans.

12. Here, the authors found that PCSK9 expression was increased in periodontitis patients and Porphyromonas gingivalis (Pg)-infected mice. Loss of PCSK9 attenuated Pg-induced periodontal bone loss in mice.

13. Results indicate a positive correlation between plasma PCSK9 and sdLDL in a community-dwelling cohort, but not in type 2 diabetic subpopulation, after confounder adjustment.

14. The presence of multiple PCSK9 LOF alleles decreased the risk of 1-year death or IRR in sepsis survivors. Biological measures suggest this may be related to an enhanced resolution of the initial infection.

15. High PCSK9 expression is associated with atherosclerosis and liver cancer.

16. PCSK9 proteolysis acts as a commonly perturbed but critical switch in controlling lipid homeostasis.

17. Data indicate the association of proprotein convertase subtilisin kexin type 9 (PCSK9) A/G (rs505151) single nucleotide polymorphisms (SNPs) with coronary artery disease (CAD) risk in the north Indian population.

18. Mutation spectrum and genotype-phenotype correlation was analyzed in patients with familial hypercholesterolemia in Chinese population.

19. Given that overexpression of these LOF PCSK9 variants does not cause UPR activation under normal homeostatic conditions, therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in the ER represent a viable strategy for reducing circulating PCSK9

20. PCSK9 was inconsistently associated with cardiovascular (CV) events in populations with type 2 diabetes. The association may depend on the level of CV risk and the background treatment.

Mouse (Murine) Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) interaction partners

1. The absence of PCSK9 in LDb mice results in decreased lipid and apoB levels, fewer atherogenic LDLs, and marked reduction of atherosclerosis.

2. In this study, the appropriate virus-like particle (VLP)-peptide vaccines targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) were screened...PCSK9Qbeta-003 vaccine obviously decreased plasma total cholesterol in both Balb/c mice and LDLR(+/-) mice

3. In the present study, it was investigated whether ticagrelor reduces oxidized lowdensity lipoprotein (oxLDL)induced endothelial cell apoptosis, an initial step for the development of atherosclerosis(AS), and alleviates AS in apolipoproteinEdeficient (ApoE/) mice by inhibiting the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9)

4. We observed long-term postnatal persistence of edited cells in both models, with reduction of plasma PCSK9 and cholesterol levels following in utero Pcsk9 targeting and rescue of the lethal phenotype of hereditary tyrosinemia type 1 following in utero Hpd targeting

5. High PCSK9 expression is associated with atherosclerosis and liver cancer.

6. Given that overexpression of these LOF PCSK9 variants does not cause UPR activation under normal homeostatic conditions, therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in the ER represent a viable strategy for reducing circulating PCSK9

7. Data suggest that expression of Pcsk9 and Ldlr in liver and pancreas can be regulated by dietary measures; here, dietary supplementation with quercetin-3-glucoside modulates expression of Pcsk9 and Ldlr in prevention of hyperlipidemia and hyperinsulinemia induced by high dietary cholesterol. (Pcsk9 = proprotein convertase subtilisin/kexin type-9; Ldlr = low-density lipoprotein receptor)

8. The data of the present study demonstrated that the PCSK9 shRNAmediated antiapoptotic effect induced by MCAO in hyperlipidemic mice is associated with ApoER2 downregulation, which may be a potential new therapy for stroke treatment in patients with hyperlipidemia.

9. It was concluded that quercetin inhibits oxLDLinduced lipid droplets in RAW264.7 cells by upregulation of ABCAl, ABCG1, LXRalpha and downregulation of PCSK9, p53, p21 and p16.

10. PCSK9 overexpression in the aorta may promote acute aortic dissection.

11. Genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation.

12. The present study aimed to explore the direct toxicity of proprotein convertase subtilisin/kexin type 9 (PCSK9) to atherosclerosis (AS) and its association with apoptotic endothelial cells.

13. present anti-PCSK9 vaccine induced long-lasting anti-PCSK9 antibody production and improved lipoprotein profiles. Thus, anti-PCSK9 vaccine could become a new option for the treatment of dyslipidemia as a long-acting therapy in future

14. PCSK9 may act as an inflammatory mediator in the pathogenesis of atherosclerosis via TLR4/NF-kappaB signaling pathway.

15. PCSK9, by sustaining smooth muscle cell synthetic phenotype, proliferation, and migration, may play a pro-atherogenic role in the arterial wall

16. PCSK9 inhibits lipoprotein(a) clearance through the LDLR.

17. Use Crispr-Cas system to introduce nonsense variants into PCSK9 to lower blood cholesterol levels.

18. Studied the combination model of a single AAV-PCSK9 injection, high-fat diet, and partial carotid ligation which induces robust atherosclerosis in the flow-disturbed carotid artery within 3 weeks in C57 mice, and results suggest this is a quick and convenient model to study atherosclerosis and mechanisms using any knockout or transgenic mice without having to generate double knockouts.

19. These observations suggest positive feedback interplay between SMC-derived PCSK9 and mtDNA damage in the proinflammatory milieu involving mtROS. This interaction results in cellular injury, characterized by apoptosis-a hallmark of atherosclerosis.

20. AdipoR activation by agonists regulated PCSK9 expression and inhibits atherosclerosis in apoE(-/-) mice.

Pig (Porcine) Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) interaction partners

1. the PCSK9-gain-of-function mutation induces rapid development of atherosclerosis in peripheral vessels of Ossabaw pigs, which is exacerbated by a high-cholesterol diet.