Abstract

While there is evidence that chronic inflammation and infection promotes plaque formation, acute infections are associated with a transient five-fold increased risk of unstable coronary and vascular syndromes caused by platelet dependent thrombosis. While many strains of bacteria induce platelet aggregation, the mechanisms by which bacteria stimulate platelets has had minimal investigation. In preliminary data utilizing comprehensive microarray analyses, and a large community cohort of almost 2,000 subjects, we found distinct patterns of platelet gene expression in patients with cardiovascular disease. While several TLRs were detected in platelets, the expression of TLR2 and IL1R in particular were increased in patients with cardiovascular disease. Importantly, the functionality of TLR in platelets was established as incubation of platelets with TLR2 ligands dose-dependently induced platelet activation and aggregation. In addition, we found enhanced platelet function and platelet-monocyte/neutrophil binding with C. pneumoniae infection in vivo, and P. gingivalis incubation. The central hypothesis of the overall program project is that

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078894-04
Application #
8527671
Study Section
Special Emphasis Panel (ZAI1-PRJ-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$230,976
Indirect Cost
$17,728

  Institution

Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Papadopoulos, G; Shaik-Dasthagirisaheb, Y B; Huang, N et al. (2017) Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol 32:250-261
Kramer, Carolyn D; Simas, Alexandra M; He, Xianbao et al. (2017) Distinct roles for dietary lipids and Porphyromonas gingivalis infection on atherosclerosis progression and the gut microbiota. Anaerobe 45:19-30
Shaik-Dasthagirisaheb, Yazdani B; Mekasha, Samrawit; He, Xianbao et al. (2016) Signaling events in pathogen-induced macrophage foam cell formation. Pathog Dis 74:
Koupenova, Milka; Mick, Eric; Mikhalev, Ekaterina et al. (2015) Sex differences in platelet toll-like receptors and their association with cardiovascular risk factors. Arterioscler Thromb Vasc Biol 35:1030-7
He, Xianbao; Liang, Yanmei; LaValley, Michael P et al. (2015) Comparative analysis of the growth and biological activity of a respiratory and atheroma isolate of Chlamydia pneumoniae reveals strain-dependent differences in inflammatory activity and innate immune evasion. BMC Microbiol 15:228
Huang, N; Shaik-Dasthagirisaheb, Y B; LaValley, M P et al. (2015) Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss. Mol Oral Microbiol 30:438-50
Beaulieu, Lea M; Clancy, Lauren; Tanriverdi, Kahraman et al. (2015) Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans. PLoS One 10:e0131688
Shaik-Dasthagirisaheb, Y B; Huang, N; Weinberg, E O et al. (2015) Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated genes following stimulation with Porphyromonas gingivalis. J Periodontal Res 50:89-102
El-Awady, Ahmed R; Miles, Brodie; Scisci, Elizabeth et al. (2015) Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk. PLoS Pathog 10:e1004647
Kramer, Carolyn D; Weinberg, Ellen O; Gower, Adam C et al. (2014) Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet. BMC Genomics 15:1176

Showing the most recent 10 out of 30 publications