Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.

Abstract

BACKGROUND: Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. METHODS: A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. RESULTS: In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). CONCLUSIONS: A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0132259

Publication Info

Rose, Jason J, Deepak Voora, Derek D Cyr, Joseph E Lucas, Aimee K Zaas, Christopher W Woods, L Kristin Newby, William E Kraus, et al. (2015). Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One, 10(7). p. e0132259. 10.1371/journal.pone.0132259 Retrieved from https://hdl.handle.net/10161/12503.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Voora

Deepak Voora

Associate Professor of Medicine
Zaas

Aimee Kirsch Zaas

Professor of Medicine

Medical education
Genomic applications for diagnosis of infectious diseases
Genomic applications for prediction of infectious diseases

Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health

1. Emerging Infections
2. Global Health
3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics
5. Bioterrorism Preparedness
6. Surveillance for communicable diseases
7. Antimicrobial resistance

Newby

Laura Kristin Newby

Professor of Medicine

Research Description

General Focus: Clinical investigation the process and treatment of acute and chronic coronary artery disease and systems issues for delivery of care to patients with these illnesses. Particular interests include management of patients with chest pain and unstable angina, evaluation of the use of biochemical markers other than CK-MB for diagnosis and risk stratification in these patients, issues related to coronary artery disease in women, and systems issues regarding optimizing the process of delivery of care to patients with acute and chronic coronary artery disease. Finally, I have a strong interest in defining the genetic contribution to development of coronary artery disease.


Key words: coronary artery disease acute myocardial infarction unstable angina chest pain women biochemical markers risk stratification genetics

Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine

Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.