Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice

Scientific Reports
Hui WangDaniel T Eitzman

Abstract

The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9 -/-) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9 -/- mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9 -/- mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9 -/- mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.

References

Feb 26, 1997·JAMA : the Journal of the American Medical Association·S Z GoldhaberC H Hennekens
Oct 23, 1997·Thrombosis Research·T KawasakiM Monden
Jul 15, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·D T EitzmanD Ginsburg
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 18, 2002·Journal of Cellular and Molecular Medicine·C Stancu, A Sima
Jul 9, 2002·British Journal of Haematology·Amparo VayáJusto Aznar
Dec 5, 2003·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Maria Teresa SartoriAntonio Girolami
Mar 10, 2005·The New England Journal of Medicine·John C LaRosaUNKNOWN Treating to New Targets (TNT) Investigators
Apr 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shirya RashidJay D Horton
Mar 24, 2006·The New England Journal of Medicine·Jonathan C CohenHelen H Hobbs
Nov 11, 2008·The New England Journal of Medicine·Paul M RidkerUNKNOWN JUPITER Study Group
Mar 31, 2009·The New England Journal of Medicine·Robert J GlynnPaul M Ridker
Mar 28, 2012·The Journal of Experimental Medicine·Marie-Luise von BrühlSteffen Massberg
Apr 13, 2012·Lancet·Samuel Z Goldhaber, Henri Bounameaux
Jul 6, 2012·Nature·Partha DuttaMatthias Nahrendorf
Apr 1, 2014·The New England Journal of Medicine·Dirk J BlomUNKNOWN DESCARTES Investigators
Jul 26, 2016·Frontiers in Immunology·Andrew S KimballPeter K Henke
Nov 16, 2016·JAMA : the Journal of the American Medical Association·Stephen J NichollsSteven E Nissen
Dec 7, 2016·Frontiers in Immunology·Volker BrinkmannArturo Zychlinsky

❮ Previous
Next ❯

Citations

Jul 12, 2018·Current Opinion in Lipidology·Theodosios D FilippatosMoses S Elisaf
Apr 10, 2021·Frontiers in Cardiovascular Medicine·Aureli LuqueroMaria Borrell-Pages
Jun 3, 2021·International Journal of Molecular Sciences·Cristina BaraleIsabella Russo
May 22, 2021·The American Journal of Pathology·Chiara MacchiMassimiliano Ruscica
Jun 3, 2021·Life·Piotr PęczekAleksandra Gąsecka
Aug 28, 2021·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Bayan Moustafa, Fernando D Testai
Oct 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Suzanne Schol-GelokJorie Versmissen

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Software Mentioned

MetaMorph Premier
7000 System SDS
NIH ImageJ

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.