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Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic coronary artery disease
Author(s) -
Rath Dominik,
UngernSternberg Saskia,
Heinzmann David,
Sigle Manuel,
Monzien Mona,
Horstmann Katja,
Schaeffeler Elke,
Winter Stefan,
Müller Karin,
GrogaBada Patrick,
Zdanyte Monika,
Borst Oliver,
Zernecke Alma,
Gawaz Meinrad,
Martus Peter,
Schwab Matthias,
Geisler Tobias,
Seizer Peter
Publication year - 2020
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14635
Subject(s) - coronary artery disease , medicine , cardiology , cyclophilin a , platelet , disease , biology , microbiology and biotechnology
Background Cyclophilin A (Cy PA ) is an important intracellular molecule mediating essential cellular functions such as signaling and protein folding. Enhanced Cy PA platelet surface expression is associated with hypertension and hypercholesterolemia in patients with stable coronary artery disease ( CAD ). In patients with acute myocardial infarction Cy PA platelet surface expression is significantly decreased. The aim of this study was to investigate possible associations of Cy PA platelet surface expression and a clinically relevant Cy PA single‐nucleotide polymorphism (Cy PA PPIA rs6850) with prognosis in patients with symptomatic cardiovascular disease. Materials and methods Blood was obtained from 335 consecutive patients with symptomatic CAD . All patients were followed up for 1080 days for endpoints all‐cause death, myocardial infarction ( MI ), ischemic stroke, and bleeding. The primary combined endpoint was defined as a composite of all‐cause death and/or MI and/or ischemic stroke. Cy clophilin A platelet surface expression levels less than or equal to the median were significantly associated with a worse prognosis (combined endpoint and all‐cause death) when compared to Cy PA greater than the median. Genotyping for Cy PA PPIA rs6850 was performed in 752 patients with symptomatic CAD . Homozygous carriers of the minor allele showed a significantly worse cumulative event‐free survival for both combined endpoint and MI when compared to carriers of the major allele. Conclusion The Cy PA platelet surface expression is associated with mortality whereas Cy PA PPIA rs6850 is associated with recurrent MI in patients with symptomatic CAD . Cy clophilin A might offer a new biomarker for risk stratification and tailoring therapies in patients with cardiovascular disease.