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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

Distribution of platelet GES score by time point in the H1N1 exposure cohort.Individual platelet gene expression signature values (platelet GES, y-axis) are plotted over time (hours, x-axis) following H1N1 viral exposure and by symptom status (symptomatic/dashed thin lines; asymptomatic/solid thin lines). Prediction curves (thick lines) for the symptomatic (dashed) vs. asymptomatic (solid) subsets are plotted based on predictions made from mixed-effects regression model (see Methods). P-values represent the association between platelet GES over time and differences over time between symptomatic vs. asymptomatic subjects.
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pone.0132259.g003: Distribution of platelet GES score by time point in the H1N1 exposure cohort.Individual platelet gene expression signature values (platelet GES, y-axis) are plotted over time (hours, x-axis) following H1N1 viral exposure and by symptom status (symptomatic/dashed thin lines; asymptomatic/solid thin lines). Prediction curves (thick lines) for the symptomatic (dashed) vs. asymptomatic (solid) subsets are plotted based on predictions made from mixed-effects regression model (see Methods). P-values represent the association between platelet GES over time and differences over time between symptomatic vs. asymptomatic subjects.

Mentions: Exposure to HIN1 was associated with an increasing platelet GES over time (time course p-value = 1e-04) (Fig 3). To confirm that the individual genes represented by the platelet GES also changed in response to H1N1 exposure we tested each probe set within the signature and found that, 40 of 50 probe sets were significantly (p < 0.05) up regulated in response to H1N1 viral exposure (S1 Fig). When comparing the symptomatic vs. asymptomatic subsets, we observed that symptomatic subjects differed at baseline with no significant differences across time (Fig 3, symptom by time interaction p-value = 0.1).


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)

Distribution of platelet GES score by time point in the H1N1 exposure cohort.Individual platelet gene expression signature values (platelet GES, y-axis) are plotted over time (hours, x-axis) following H1N1 viral exposure and by symptom status (symptomatic/dashed thin lines; asymptomatic/solid thin lines). Prediction curves (thick lines) for the symptomatic (dashed) vs. asymptomatic (solid) subsets are plotted based on predictions made from mixed-effects regression model (see Methods). P-values represent the association between platelet GES over time and differences over time between symptomatic vs. asymptomatic subjects.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132259.g003: Distribution of platelet GES score by time point in the H1N1 exposure cohort.Individual platelet gene expression signature values (platelet GES, y-axis) are plotted over time (hours, x-axis) following H1N1 viral exposure and by symptom status (symptomatic/dashed thin lines; asymptomatic/solid thin lines). Prediction curves (thick lines) for the symptomatic (dashed) vs. asymptomatic (solid) subsets are plotted based on predictions made from mixed-effects regression model (see Methods). P-values represent the association between platelet GES over time and differences over time between symptomatic vs. asymptomatic subjects.
Mentions: Exposure to HIN1 was associated with an increasing platelet GES over time (time course p-value = 1e-04) (Fig 3). To confirm that the individual genes represented by the platelet GES also changed in response to H1N1 exposure we tested each probe set within the signature and found that, 40 of 50 probe sets were significantly (p < 0.05) up regulated in response to H1N1 viral exposure (S1 Fig). When comparing the symptomatic vs. asymptomatic subsets, we observed that symptomatic subjects differed at baseline with no significant differences across time (Fig 3, symptom by time interaction p-value = 0.1).

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