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The glucocorticoid ...
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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- Jönsson, Simon (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet
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- Lundberg, Anna K (författare)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet
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- Jonasson, Lena (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Kardiologiska kliniken US
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Matrix metalloproteinase
- glucocorticoid
- glucocorticoid receptor
- leukocyte
- coronary artery disease
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)