- •LPS uptake in HUVECs is dose-dependent on LDL concentration.
- •PCSK9 dose-dependently inhibits LDLR-mediated endocytosis of LPS in HUVECs.
- •Decreased PCSK9 increases endothelial cell LPS uptake and proinflammatory response.
Methods and results
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia.Hum. Mutat. 2005; 26: 497
- Plasma PCSK9 preferentially reduces liver LDL receptors in mice.J. Lipid Res. 2008; 49: 1303-1311
- PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells.Curr. Opin. Lipidol. 2014; 25: 387-393
- Receptor-mediated endocytosis: concepts emerging from the LDL receptor system.Annu. Rev. Cell Biol. 1985; 1: 1-39
- Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.J. Clin. Invest. 2006; 116: 2995-3005
- Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.N. Engl. J. Med. 2006; 354: 1264-1272
- Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.Nat. Genet. 2008; 40: 189-197
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N. Engl. J. Med. 2017; 376: 1713-1722
- Distribution and kinetics of lipoprotein-bound endotoxin.Infect. Immun. 2001; 69: 2821-2828
- Lipid composition and lipopolysaccharide binding capacity of lipoproteins in plasma and lymph of patients with systemic inflammatory response syndrome and multiple organ failure.Crit. Care Med. 2003; 31: 1647-1653
- Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein.Infect. Immun. 2005; 73: 2321-2326
- PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Sci. Transl. Med. 2014; 6: 258ra143
- Lipopolysaccharide is cleared from the circulation by hepatocytes via the low density lipoprotein receptor.PLoS One. 2016; 11e0155030
- Expression of the VLDL receptor in endothelial cells.Arterioscler. Thromb. Vasc. Biol. 1996; 16: 407-415
- Oxidized LDL through LOX-1 modulates LDL-receptor expression in human coronary artery endothelial cells.Biochem. Biophys. Res. Commun. 2003; 307: 1008-1012
- Endothelial transcytosis of lipoproteins in atherosclerosis.Front Cardiovasc Med. 2018; 5: 130
- Triciribine increases LDLR expression and LDL uptake through stabilization of LDLR mRNA.Sci. Rep. 2018; 816174
- The central role of Proprotein convertase subtilisin/kexin type 9 in septic pathogen lipid transport and clearance.Am. J. Respir. Crit. Care Med. 2015; 192: 1275-1286
- Differential expression of PCSK9 modulates infection, inflammation, and coagulation in a murine model of sepsis.Shock. 2016; 46: 672-680
- Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates.Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 11915-11920
- Endothelial function.Circulation. 2011; 124: e906-e912
- Vascular endothelium in atherosclerosis.Cell Tissue Res. 2009; 335: 191-203
- Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients.Clin. J. Am. Soc. Nephrol. 2008; 3: 431-436
- Effects of intra-abdominal sepsis on atherosclerosis in mice.Crit. Care. 2014; 18: 469
- CD36 differently regulates macrophage responses to smooth and rough lipopolysaccharide.PLoS One. 2016; 11e0153558
- Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2.Trends Microbiol. 2004; 12: 186-192
- Inflammatory caspases are innate immune receptors for intracellular LPS.Nature. 2014; 514: 187-192
- Noncanonical inflammasome activation by intracellular LPS independent of TLR4.Science. 2013; 341: 1246-1249
- Bacterial outer membrane vesicles mediate cytosolic localization of LPS and caspase-11 activation.Cell. 2016; 165: 1106-1119
- Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in Gram positive septic shock patients.Sci. Rep. 2019; 910588