Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients

Yueh Chung Chen, Feng Yen Lin, Yi Wen Lin, Shu Meng Cheng, Chao Chien Chang, Rong Ho Lin, Chun Ling Chuang, Jehn Shing Sheu, Shan Min Chen, Chien Sung Tsai

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Abstract

Purpose: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. Methods: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. Clinical Trial Registration: NCT02101437.

Original languageEnglish
JournalCardiovascular Drugs and Therapy
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

MicroRNAs
Coronary Artery Disease
Blood Platelets
clopidogrel
Therapeutics
Stents
Percutaneous Coronary Intervention
ROC Curve
Pharmaceutical Preparations
Aspirin
Heart Diseases
Healthy Volunteers
Clinical Trials

Keywords

  • Antiplatelet therapy
  • miRNA
  • P2Y12
  • Platelet reactivity unit
  • SYNTAX score

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients. / Chen, Yueh Chung; Lin, Feng Yen; Lin, Yi Wen; Cheng, Shu Meng; Chang, Chao Chien; Lin, Rong Ho; Chuang, Chun Ling; Sheu, Jehn Shing; Chen, Shan Min; Tsai, Chien Sung.

In: Cardiovascular Drugs and Therapy, 01.01.2019.

Research output: Contribution to journalArticle

Chen, Yueh Chung ; Lin, Feng Yen ; Lin, Yi Wen ; Cheng, Shu Meng ; Chang, Chao Chien ; Lin, Rong Ho ; Chuang, Chun Ling ; Sheu, Jehn Shing ; Chen, Shan Min ; Tsai, Chien Sung. / Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients. In: Cardiovascular Drugs and Therapy. 2019.
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abstract = "Purpose: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. Methods: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3{\%} and 90.0{\%}, respectively) and specificity (71.4{\%} and 93.3{\%}) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. Clinical Trial Registration: NCT02101437.",
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AU - Chen, Yueh Chung

AU - Lin, Feng Yen

AU - Lin, Yi Wen

AU - Cheng, Shu Meng

AU - Chang, Chao Chien

AU - Lin, Rong Ho

AU - Chuang, Chun Ling

AU - Sheu, Jehn Shing

AU - Chen, Shan Min

AU - Tsai, Chien Sung

PY - 2019/1/1

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N2 - Purpose: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. Methods: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. Clinical Trial Registration: NCT02101437.

AB - Purpose: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. Methods: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. Clinical Trial Registration: NCT02101437.

KW - Antiplatelet therapy

KW - miRNA

KW - P2Y12

KW - Platelet reactivity unit

KW - SYNTAX score

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