title: Impact of atrial fibrillation on platelet gene expression.
abstract: OBJECTIVE
  Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR).
  
  
  RESULTS
  RNA from isolated platelets were reverse transcribed, assayed against 15 genes using real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin-like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold-lower (17.0±2.8 vs 12.5±3.8, P<.001), follow by genes encoding for prostacyclin receptor, and for von Willebrand factor which had fourfold lower expression compared to NSR controls. Gender, type of atrial fibrillation, heart failure, hypertension, prior stroke, diabetes mellitus, and atherosclerosis were associated with different gene expression. Following PVI, expression of four genes significantly increased, particularly IGFALS gene (increased 256-fold) and ADAMT gene increased 16-fold); expression of three genes significantly decreased, and expression of eight genes has not changed.
  
  
  CONCLUSIONS
  Platelets are capable to respond to the circulatory environment of NVAF by altering transcript and changing prothrombotic status. This shows platelet potential for molecular "reprogramming" possibly induced by flow disturbances of NVAF.
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Waldemar E
authors.identifier: http://orcid.org/0000-0002-8119-6206
authors.initials: WE
authors.lastname: Wysokinski
authors.affiliation: Department of Cardiovascular Medicine, Vascular Surgery and Medicine Section, NorthShore University HealthSystem, Skokie, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Tafur
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Naser
authors.initials: N
authors.lastname: Ammash
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Asirvatham
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: University Medical School of Wroclaw, Wroclaw, Poland.
authors.forename: Izabella
authors.initials: I
authors.lastname: Gosk-Bierska
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Grill
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Slusser
authors.affiliation: Department of Internal Medicine, University of Kansas, School of Medicine-Wichita, Wichita, KS, USA.
authors.forename: Jozef
authors.initials: J
authors.lastname: Mruk
authors.affiliation: Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: McBane
mesh_terms: D000071120:ADAMTS13 Protein / Q000097:blood / Q000235:genetics; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D001281:Atrial Fibrillation / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000097:blood / Q000235:genetics; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011667:Pulmonary Veins / Q000601:surgery; D044006:Receptors, Epoprostenol / Q000097:blood / Q000235:genetics; D012737:Sex Factors; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C113936:PTGIR protein, human; D044006:Receptors, Epoprostenol; C075944:insulin-like growth factor binding protein, acid labile subunit; D014841:von Willebrand Factor; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: gene expression; platelets; pulmonary vein isolation; thrombosis