oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Platelet activation triggered by Chlamydia pneumoniae is antagonized by 12-lipoxygenase inhibitors but not cyclooxygenase inhibitors
Division of Pharmacology, Department of Medicine and Care, Cardiovascular Inflammation Research Centre, Linköping, Sweden.
Division of Pharmacology, Department of Medicine and Care, Cardiovascular Inflammation Research Centre, Linköping, Sweden.
Division of Pharmacology, Department of Medicine and Care, Cardiovascular Inflammation Research Centre, Linköping, Sweden.
Division of Pharmacology, Department of Medicine and Care, Cardiovascular Inflammation Research Centre, Linköping, Sweden.
2007 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 566, no 1-3, 20-27 p.Article in journal (Refereed) Published
Abstract [en]

Chlamydia pneumoniae is a respiratory pathogen that has been linked to cardiovascular disease. We have recently shown that C. pneumoniae activates platelets, leading to oxidation of low-density lipoproteins. The aim of the present study was to evaluate the inhibitory effects of different pharmacological agents on platelet aggregation and secretion induced by C. pneumoniae. Platelet interaction with C. pneumoniae was studied by analyzing platelet aggregation and ATP-secretion with Lumi-aggregometry. Platelet aggregation and ATP-secretion induced by C. pneumoniae was markedly inhibited by the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP), an effect that was counteracted by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Pre-treatment of platelets with the 12-lipoxygenase (12-LOX) inhibitors cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC) and 5,6,7-trikydroxyflavone (baicalein) completely blocked the activation, whereas the cyclooxygenase (COX) inhibitors 2-acetyloxybenzoic acid (aspirin) and (8E)-8-[hydroxy-(pyridin-2-ylamino)methylidene]-9-methyl-10,10-dioxo-10$l;(6)thia-9-azabicyclo[4.4.0]deca-1,3,5-trien-7-one (piroxicam) had no inhibitory effects. Opposite to C. pneumoniae-induced activation, platelets stimulated by collagen were inhibited by the COX-inhibitors but were unaffected by the 12-LOX-inhibitors. The platelet activating factor (PAF) antagonist Ginkgolide B blocked the C. pneumoniae-induced platelet activation, whereas the responses to collagen were unaffected. Furthermore, the P2Y1 and P2Y12 purinergic receptor antagonists 2'-deoxy-N6-methyladenosine 3',5'-bisphosphate (MRS2179) and N(6)-(2-methyl-thioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma-dichloromethylene-ATP (cangrelor) inhibited the aggregation and secretion caused by C. pneumoniae. It is well-known that the efficacy of COX inhibitors in the prevention and treatment of cardiovascular disease varies between different patients, and that patients with low responses to aspirin have a higher risk to encounter cardiovascular events. The findings in this study showing that platelets stimulated by C. pneumoniae are unaffected by COX inhibitors but sensitive to 12-LOX inhibitors, may thus be of importance in future management of atherosclerosis and thrombosis.

Place, publisher, year, edition, pages
Elsevier, 2007. Vol. 566, no 1-3, 20-27 p.
Keyword [en]
Chlamydia pneumoniae; platelet; aggregation; lipoxygenase; cyclooxygenase
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-56660DOI: 10.1016/j.ejphar.2007.03.024ISI: 000247281600003PubMedID: 17459368ScopusID: 2-s2.0-34249274950OAI: oai:DiVA.org:oru-56660DiVA: diva2:1083503
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2017-04-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Kälvegren, HannaGrenegård, MagnusBengtsson, Torbjörn
In the same journal
European Journal of Pharmacology
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 7 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf