Rose, JJ and Voora, D and Cyr, DD and Lucas, JE and Zaas, AK and Woods, CW and Newby, LK and Kraus, WE and Ginsburg, GS
(2015)
Gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction.
PLoS ONE, 10 (7).
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.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Rose, JJ | jjr85@pitt.edu | JJR85 | | Voora, D | | | | Cyr, DD | | | | Lucas, JE | | | | Zaas, AK | | | | Woods, CW | | | | Newby, LK | | | | Kraus, WE | | | | Ginsburg, GS | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Schulz, Christian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
20 July 2015 |
Date Type: |
Publication |
Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
Journal or Publication Title: |
PLoS ONE |
Volume: |
10 |
Number: |
7 |
DOI or Unique Handle: |
10.1371/journal.pone.0132259 |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Medicine > Critical Care Medicine |
Refereed: |
Yes |
Date Deposited: |
23 Aug 2016 14:25 |
Last Modified: |
02 Feb 2019 12:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/28416 |
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