Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation: Effect of pulmonary veins isolation

Waldemar E. Wysokinski, Alfonso Tafur, Yanhong Wu, Naser Ammash, Samuel J Asirvatham, Izabela Gosk-Bierska, Diane E. Grill, Joshua P. Slusser, Jozef Mruk, Robert D. Mcbane

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Cardiovascular Electrophysiology
DOIs
StateAccepted/In press - Jan 1 2018

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Pulmonary Veins
Atrial Fibrillation
Blood Platelets
Gene Expression
Genes
Platelet Count
Actin Depolymerizing Factors
beta 2-Microglobulin
Flow Cytometry

Keywords

  • Atrial fibrillation
  • Gene expression
  • Reticulated platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation : Effect of pulmonary veins isolation. / Wysokinski, Waldemar E.; Tafur, Alfonso; Wu, Yanhong; Ammash, Naser; Asirvatham, Samuel J; Gosk-Bierska, Izabela; Grill, Diane E.; Slusser, Joshua P.; Mruk, Jozef; Mcbane, Robert D.

In: Journal of Cardiovascular Electrophysiology, 01.01.2018.

Research output: Contribution to journalArticle

Wysokinski, Waldemar E. ; Tafur, Alfonso ; Wu, Yanhong ; Ammash, Naser ; Asirvatham, Samuel J ; Gosk-Bierska, Izabela ; Grill, Diane E. ; Slusser, Joshua P. ; Mruk, Jozef ; Mcbane, Robert D. / Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation : Effect of pulmonary veins isolation. In: Journal of Cardiovascular Electrophysiology. 2018.
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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.",
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T1 - Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation

T2 - Effect of pulmonary veins isolation

AU - Wysokinski, Waldemar E.

AU - Tafur, Alfonso

AU - Wu, Yanhong

AU - Ammash, Naser

AU - Asirvatham, Samuel J

AU - Gosk-Bierska, Izabela

AU - Grill, Diane E.

AU - Slusser, Joshua P.

AU - Mruk, Jozef

AU - Mcbane, Robert D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Atrial fibrillation

KW - Gene expression

KW - Reticulated platelets

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DO - 10.1111/jce.13438

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