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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

Genes upregulated and downregulated at week 9 in ApoE-/- mice with bacterial infection or a Western diet.Heatmap shows the transcripts identified through microarray as upregulated or downregulated 2-fold or more by infection with P. gingivalis (Pg), C. pneumoniae (Cp), or fed a Western diet (WD) compared to Untreated Control in the ApoE-/- Mice. Each condition represents RNA from 3 mice pooled.
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pone.0131688.g002: Genes upregulated and downregulated at week 9 in ApoE-/- mice with bacterial infection or a Western diet.Heatmap shows the transcripts identified through microarray as upregulated or downregulated 2-fold or more by infection with P. gingivalis (Pg), C. pneumoniae (Cp), or fed a Western diet (WD) compared to Untreated Control in the ApoE-/- Mice. Each condition represents RNA from 3 mice pooled.

Mentions: Nine weeks following the last infection with P. gingivalis, C. pneumoniae, or 9 weeks of feeding a Western diet, ApoE-/- mice were sacrificed in order to understand the changes in platelet transcripts before the formation of overt plaques. Following P. gingivalis infection, only 41 genes were increased and 32 were decreased (Fig 2). The top 5 genes that exhibited increased expression were MFAP1A (5.31-fold), TRBV4 (4.21-fold), POLR2C (3.99-fold), CIDEC (3.97-fold), and SMS (3.75-fold). Top 5 genes that exhibited decreased expression were S100A8 (-4.15-fold), S100A9 (-4.08-fold), OLFR135 (-3.45-fold), FCF1 (-3.26-fold), and AGK (-3.01-fold). GSEA identified numerous gene sets positively enriched, including coagulation and signaling pathways; however, these gene sets were not significantly altered by P. gingivalis infection (NES >-2, FDR q >0.05; S5 Table). It was the negatively enriched gene sets that were more significantly affected, including RNA/gene expression (NES ≤-2, Nom p <0.05, FDR q <0.05; S6 Table).


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)

Genes upregulated and downregulated at week 9 in ApoE-/- mice with bacterial infection or a Western diet.Heatmap shows the transcripts identified through microarray as upregulated or downregulated 2-fold or more by infection with P. gingivalis (Pg), C. pneumoniae (Cp), or fed a Western diet (WD) compared to Untreated Control in the ApoE-/- Mice. 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.g002: Genes upregulated and downregulated at week 9 in ApoE-/- mice with bacterial infection or a Western diet.Heatmap shows the transcripts identified through microarray as upregulated or downregulated 2-fold or more by infection with P. gingivalis (Pg), C. pneumoniae (Cp), or fed a Western diet (WD) compared to Untreated Control in the ApoE-/- Mice. Each condition represents RNA from 3 mice pooled.
Mentions: Nine weeks following the last infection with P. gingivalis, C. pneumoniae, or 9 weeks of feeding a Western diet, ApoE-/- mice were sacrificed in order to understand the changes in platelet transcripts before the formation of overt plaques. Following P. gingivalis infection, only 41 genes were increased and 32 were decreased (Fig 2). The top 5 genes that exhibited increased expression were MFAP1A (5.31-fold), TRBV4 (4.21-fold), POLR2C (3.99-fold), CIDEC (3.97-fold), and SMS (3.75-fold). Top 5 genes that exhibited decreased expression were S100A8 (-4.15-fold), S100A9 (-4.08-fold), OLFR135 (-3.45-fold), FCF1 (-3.26-fold), and AGK (-3.01-fold). GSEA identified numerous gene sets positively enriched, including coagulation and signaling pathways; however, these gene sets were not significantly altered by P. gingivalis infection (NES >-2, FDR q >0.05; S5 Table). It was the negatively enriched gene sets that were more significantly affected, including RNA/gene expression (NES ≤-2, Nom p <0.05, FDR q <0.05; S6 Table).

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