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

Rose JJ, Voora D, Cyr DD, Lucas JE, Zaas AK, Woods CW, Newby LK, Kraus WE, Ginsburg GS - PLoS ONE (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Experimental Design for CATHGEN cohort.Viral GES is projected on the 594 patients from CATHGEN, then separated into positive or negative viral GES based on a previously defined cutoff (see Methods). Baseline characteristics and MI status were compared between groups. LHC—Left Heart Catheterization
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pone.0132259.g002: Experimental Design for CATHGEN cohort.Viral GES is projected on the 594 patients from CATHGEN, then separated into positive or negative viral GES based on a previously defined cutoff (see Methods). Baseline characteristics and MI status were compared between groups. LHC—Left Heart Catheterization

Mentions: To determine a “cut-off” value of viral GES to classify viral infection in the CATHGEN cohort we generated a receiver operating characteristics (ROC) curve using microarray data from the infection cohorts to discriminate between asymptomatic and symptomatic subjects (Fig 2). The area under the ROC curve in the infection cohorts was 0.91 and the optimal cutoff (calculated as the value that achieved the maximum sum of sensitivity and specificity) was a viral GES of ≥ 0.63. The distribution of the viral GES score was approximately the same in the CATHGEN (median viral GES score = -0.56 interquartile range (IQR) [-0.84, -0.23] vs. asymptomatic time points from viral infection cohorts (median viral GES = -0.51, IQR [-0.64, -0.18]. Therefore, we directly applied the cutoff derived in the viral infection cohorts to the CATHGEN data to classify individuals as having molecular evidence of viral infection (viral GES ≥ 0.63, “positive”) or no molecular evidence of viral infection (viral GES < 0.63, “negative”). Sensitivity analyses were performed by varying the cutoff level in the CATHGEN cohort.


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

Rose JJ, Voora D, Cyr DD, Lucas JE, Zaas AK, Woods CW, Newby LK, Kraus WE, Ginsburg GS - PLoS ONE (2015)

Experimental Design for CATHGEN cohort.Viral GES is projected on the 594 patients from CATHGEN, then separated into positive or negative viral GES based on a previously defined cutoff (see Methods). Baseline characteristics and MI status were compared between groups. LHC—Left Heart Catheterization
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507878&req=5

pone.0132259.g002: Experimental Design for CATHGEN cohort.Viral GES is projected on the 594 patients from CATHGEN, then separated into positive or negative viral GES based on a previously defined cutoff (see Methods). Baseline characteristics and MI status were compared between groups. LHC—Left Heart Catheterization
Mentions: To determine a “cut-off” value of viral GES to classify viral infection in the CATHGEN cohort we generated a receiver operating characteristics (ROC) curve using microarray data from the infection cohorts to discriminate between asymptomatic and symptomatic subjects (Fig 2). The area under the ROC curve in the infection cohorts was 0.91 and the optimal cutoff (calculated as the value that achieved the maximum sum of sensitivity and specificity) was a viral GES of ≥ 0.63. The distribution of the viral GES score was approximately the same in the CATHGEN (median viral GES score = -0.56 interquartile range (IQR) [-0.84, -0.23] vs. asymptomatic time points from viral infection cohorts (median viral GES = -0.51, IQR [-0.64, -0.18]. Therefore, we directly applied the cutoff derived in the viral infection cohorts to the CATHGEN data to classify individuals as having molecular evidence of viral infection (viral GES ≥ 0.63, “positive”) or no molecular evidence of viral infection (viral GES < 0.63, “negative”). Sensitivity analyses were performed by varying the cutoff level in the CATHGEN cohort.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus