title: Impact of variables of the P-selectin - P-selectin glycoprotein ligand-1 axis on leukocyte-platelet interactions in cardiovascular disease.
abstract: The formation of leukocyte-platelet aggregates (LPA), through the P-selectin - P-selectin glycoprotein ligand (PSGL)-1 axis, plays a pivotal role in atherothrombosis. In order to investigate the influence of platelet (pP-selectin) and soluble P-selectin (sP-selectin), and of variations in the genes encoding for P-selectin (SELP) and PSGL-1 (SELPLG) on LPA formation, we assessed monocyte (MPA)- and neutrophil-platelet aggregates (NPA) as well as pP-selectin by flow cytometry in 263 patients undergoing angioplasty and stenting. sP-selectin was determined by ELISA, the SELP Pro715 allele and the SELPLG Ile62 allele were determined by allele specific PCR. The Pro715 allele was significantly associated with lower levels of in vivo pP-selectin and sP-selectin, while agonists´ inducible pP-selectin was not influenced by the Pro715 allele. PP-selectin was significantly associated with MPA and NPA formation. The in vivo formation of MPA and NPA depended to 19 % and 7.4 %, respectively, on in vivo pP-selectin, irrespective of the Pro715 allele and the Ile62 allele carrier status. TRAP-6 inducible MPA and NPA depended to 34 % and 27 %, respectively, on TRAP-6 inducible pP-selectin, but were independent of the Pro715 allele carrier status. Carriers of the Ile62 allele showed a stronger correlation between TRAP-6 inducible pP-selectin and TRAP-6 inducible MPA/NPA than non-carriers. Furthermore, TRAP-6 inducible NPA were higher in Ile62 allele carriers, which suggests higher thrombin sensitivity. In conclusion, our findings point to the significant role of pP-selectin for MPA and NPA formation, while other variables like sP-selectin, the SELP Pro715 allele and the SELPLG Ile62 allele have less influence.
authors.affiliation: Thomas Gremmel, MD, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel.: +431 40400 4671, Fax: +431 40400 4665, E-mail: thomas.gremmel@meduniwien.ac.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Beate
authors.initials: B
authors.lastname: Eichelberger
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017130:Angioplasty / Q000295:instrumentation; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000628:therapy; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D019007:P-Selectin / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D010973:Platelet Adhesiveness / Q000187:drug effects; D015607:Stents; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D009842:Oligopeptides; D019007:P-Selectin; C084882:P-selectin ligand protein; C546937:SELP protein, human; C504808:Ser-Phe-Phe-Leu-Arg-Asn
keywords: P-selectin; P-selectin glycoprotein ligand-1; genotyping; leukocyte-platelet interactions