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

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

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

2. 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.

3. 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.

4. 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.

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

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

7. 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.

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

9. 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

10. 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.

11. These findings support a model in which SURF4 functions as an endoplasmic reticulum cargo receptor mediating the efficient cellular secretion of PCSK9.

12. A long-term physical activity caused increase in PCSK9 blood levels.

13. The present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with coronary artery disease risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP

14. In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters.

15. C679X loss-of-function PCSK9 variant lowers fasting glucose levels.

16. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD [Alzheimer disease]prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Conclusion: Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD [Alzheimer disease].

17. High serum PCSK9 levels predict acute coronary syndrome occurrence at 24-month follow-up after carotid endarterectomy in patients with severe carotid artery stenosis.

18. Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR.

19. HepG2 cell lines transfected with siRNA directed to PCSK9 were challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5alpha-dihydroxytestosterone (5alpha-DHT), or estradiol for 24h, leading to an overt expression of PCSK9 and down-regulated expression of LDLR.

20. Plasma PCSK9 levels and lipoprotein distribution are preserved in hypolipoproteinemia carriers.

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

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

2. 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

3. 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)

4. 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.

5. 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.

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

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

8. 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.

9. 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

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

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

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

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

14. 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.

15. 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.

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

17. Adeno-associated virus mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with angiotensin II.

18. conditions that cause ER stress regardless of their ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake.

19. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation.

20. PCSK9 increases hepatic lipid and lipoprotein production via apoE- and LDLR-dependent mechanisms

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.