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Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans.

Beaulieu LM, Clancy L, Tanriverdi K, Benjamin EJ, Kramer CD, Weinberg EO, He X, Mekasha S, Mick E, Ingalls RR, Genco CA, Freedman JE - PLoS ONE (2015)

Bottom Line: At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only.Results were reinforced in platelets obtained from participants of the FHS.Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.

View Article: PubMed Central - PubMed

Affiliation: University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, MA, United States of America.

ABSTRACT

Introduction: Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli--two bacterial infections and a Western diet--on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants).

Methods: Blood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE-/- mice were measured in platelet samples from FHS using high throughput qRT-PCR.

Results: At week 1, both bacterial infections increased circulating platelet-neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS.

Conclusion: Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.

No MeSH data available.


Related in: MedlinePlus

Verification of microarray analysis through qRT-PCR.Gene expression for MFAP1A at Week 9 identified through the microarray were verified using qRT-PCR. Each condition represents RNA from 3 mice pooled.
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pone.0131688.g003: Verification of microarray analysis through qRT-PCR.Gene expression for MFAP1A at Week 9 identified through the microarray were verified using qRT-PCR. Each condition represents RNA from 3 mice pooled.

Mentions: In mice fed a Western diet for 9 weeks, there were 67 genes increased and 67 genes decreased (Fig 2). The top 5 genes that exhibited increased expression as a result of a Western diet were TRBV4 (7.14-fold), TRAV13-3 (3.90-fold), TMX2 (3.74-fold), SMS (3.14-fold), and GNPNAT1 (3.05-fold). The top 5 genes with decreased expression with a Western diet were ALB (-18.34-fold), FABP1 (-6.89-fold), TTR (-5.51-fold), SERPINA1B (-4.95-fold), and APOA2 (-4.95-fold). Numerous gene sets were positively enriched, including those associated with DNA/proliferation, inflammation, RNA/gene expression, and signaling (NES >2, Nom p <0.05, FDR q <0.05; S9 Table). Only a few gene sets were negatively enriched, including those involved in coagulation and lipid (NES <-2, Nom p <0.01, FDR q <0.05; S10 Table). As a way to verify these results, qRT-PCR was run on week 9 samples for MFAP1A. As seen in Fig 3, there is an increase in its expression with P. gingivalis infection that is greater than the increase with C. pneumoniae infection or a Western diet, similar to the findings in the microarray.


Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans.

Beaulieu LM, Clancy L, Tanriverdi K, Benjamin EJ, Kramer CD, Weinberg EO, He X, Mekasha S, Mick E, Ingalls RR, Genco CA, Freedman JE - PLoS ONE (2015)

Verification of microarray analysis through qRT-PCR.Gene expression for MFAP1A at Week 9 identified through the microarray were verified using qRT-PCR. Each condition represents RNA from 3 mice pooled.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493099&req=5

pone.0131688.g003: Verification of microarray analysis through qRT-PCR.Gene expression for MFAP1A at Week 9 identified through the microarray were verified using qRT-PCR. Each condition represents RNA from 3 mice pooled.
Mentions: In mice fed a Western diet for 9 weeks, there were 67 genes increased and 67 genes decreased (Fig 2). The top 5 genes that exhibited increased expression as a result of a Western diet were TRBV4 (7.14-fold), TRAV13-3 (3.90-fold), TMX2 (3.74-fold), SMS (3.14-fold), and GNPNAT1 (3.05-fold). The top 5 genes with decreased expression with a Western diet were ALB (-18.34-fold), FABP1 (-6.89-fold), TTR (-5.51-fold), SERPINA1B (-4.95-fold), and APOA2 (-4.95-fold). Numerous gene sets were positively enriched, including those associated with DNA/proliferation, inflammation, RNA/gene expression, and signaling (NES >2, Nom p <0.05, FDR q <0.05; S9 Table). Only a few gene sets were negatively enriched, including those involved in coagulation and lipid (NES <-2, Nom p <0.01, FDR q <0.05; S10 Table). As a way to verify these results, qRT-PCR was run on week 9 samples for MFAP1A. As seen in Fig 3, there is an increase in its expression with P. gingivalis infection that is greater than the increase with C. pneumoniae infection or a Western diet, similar to the findings in the microarray.

Bottom Line: At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only.Results were reinforced in platelets obtained from participants of the FHS.Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.

View Article: PubMed Central - PubMed

Affiliation: University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, MA, United States of America.

ABSTRACT

Introduction: Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli--two bacterial infections and a Western diet--on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants).

Methods: Blood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE-/- mice were measured in platelet samples from FHS using high throughput qRT-PCR.

Results: At week 1, both bacterial infections increased circulating platelet-neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS.

Conclusion: Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.

No MeSH data available.


Related in: MedlinePlus