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The glucocorticoid ...
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Jönsson, SimonLinköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet
(författare)
The glucocorticoid receptor alpha isoform is overexpressed in blood mononuclear cells from patients with coronary artery disease : Evidence for increased glucocorticoid sensitivity
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LIBRIS-ID:oai:DiVA.org:liu-114324
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-114324URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:vet swepub-contenttype
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Ämneskategori:ovr swepub-publicationtype
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Context: Coronary artery disease (CAD) is characterized by low-grade chronic inflammation including leukocyte-derived overexpression of matrix metalloproteinase (MMP)-9 and its tissue inhibitors (TIMPs). The mechanisms behind this overexpression are not clarified but may involve dysregulated glucocorticoid regulation of MMP-9.Objective: We hypothesized that the increased expression of MMP-9 and TIMPs in peripheral blood mononuclear cells (PBMCs) from CAD patients was associated with reduced glucocorticoid sensitivity.Setting: This was an observational study conducted at the Outpatient Cardiology Clinic at the University Hospital, Linköping, Sweden.Participants: CAD patients with a history of non-ST-elevation myocardial infarction were consecutively included. Healthy control subjects were randomly recruited from the Swedish Population Register.Main outcome measures: We measured mRNA and protein levels of glucocorticoid receptors (GR)-α and -β in PBMCs in vivo and further investigated the effects of dexamethasone on MMP-9, TIMP, GR-α and -β expression ex vivo.Results: The GR-α mRNA levels were markedly increased in PBMCs from CAD patients, whereas GR-β mRNA levels did not differ between patients and controls. Ex vivo, the inhibitory effects of dexamethasone on MMP-9 and TIMP mRNA and protein expression were equal to or slightly higher in patients. Moreover, the dexamethasone treatment resulted in significantly reduced levels of GR-α mRNA in PBMCs.Conclusion: In contrast to our original hypothesis, we found evidence for increased glucocorticoid sensitivity in PBMCs from CAD patients. It may be suggested that the overexpression of MMP-9 and TIMPs in patients is associated with a state of relative hypocortisolism, thus contributing to a systemic low-grade inflammation.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lundberg, Anna KLinköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet(Swepub:liu)annli40
(författare)
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Jonasson, LenaÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Kardiologiska kliniken US(Swepub:liu)lenjo59
(författare)
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Linköpings universitetAvdelningen för kardiovaskulär medicin
(creator_code:org_t)
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