Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation: Effect of pulmonary veins isolation
Corresponding Author
Waldemar E. Wysokinski MD, PhD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Correspondence
Waldemar E. Wysokinski, MD, PhD, Department of Cardiovascular Medicine, Mayo Clinic and Foundation for Education and Research, 200 S.W. First Street, Rochester, MN 55905, USA.
Email: [email protected]
Search for more papers by this authorAlfonso Tafur MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorYanhong Wu PhD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorNaser Ammash MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorSamuel J. Asirvatham MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorIzabela Gosk-Bierska MD, PhD
Department of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorDiane E. Grill MS
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorJoshua P. Slusser BS
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorJozef Mruk MD, PhD
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Witchita, KS, USA
Wichita Clinic, Wichita, KS, USA
Search for more papers by this authorRobert D. McBane MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorCorresponding Author
Waldemar E. Wysokinski MD, PhD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Correspondence
Waldemar E. Wysokinski, MD, PhD, Department of Cardiovascular Medicine, Mayo Clinic and Foundation for Education and Research, 200 S.W. First Street, Rochester, MN 55905, USA.
Email: [email protected]
Search for more papers by this authorAlfonso Tafur MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorYanhong Wu PhD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorNaser Ammash MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorSamuel J. Asirvatham MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorIzabela Gosk-Bierska MD, PhD
Department of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorDiane E. Grill MS
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorJoshua P. Slusser BS
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorJozef Mruk MD, PhD
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Witchita, KS, USA
Wichita Clinic, Wichita, KS, USA
Search for more papers by this authorRobert D. McBane MD
Department of Cardiovascular Medicine, Mayo Clinic Foundation for Education and Research, Rochester, MN, USA
Search for more papers by this authorFunding information:
This work was supported by CR20 # 91121 grant, and Technology Access Funding from the Department of Internal Medicine, Mayo Clinic. Statistical support was provided by an internal grant from the Mayo Clinic Division of Cardiology.
Disclosures: None.
Abstract
Introduction
Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes.
Methods and results
Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3–4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9 vs. 5.7 ± 1.6, P < 0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0 vs. 6.7+5.4, P < 0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged.
Conclusions
NVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.
Supporting Information
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