liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
Overexpression of MMP-9 and Its Inhibitors in Blood Mononuclear Cells after Myocardial Infarction - Is It Associated with Depressive Symptomatology?
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, e105572- p.Article in journal (Refereed) Published
Abstract [en]

Background: Matrix metalloproteinase (MMP)-9 may play a central role in the development and progression of atherosclerosis. Emerging evidence also indicates an association between MMP-9 and depressive symptomatology. Here, we investigated whether expression of MMP-9 and its inhibitors in blood mononuclear cells and plasma were related to depressive symptoms in patients with a recent myocardial infarction (MI). Methods and Results: Blood sampling was performed between 6 and 18 months after MI in 57 patients. Forty-one clinically healthy subjects were included as controls. Gene expression of MMP-9 and its main tissue inhibitors TIMP-1 and -2 were analyzed in freshly isolated or cultured blood mononuclear cells. Corresponding protein levels were assessed in cell supernatants and plasma. In post-MI patients, mRNA levels of MMP-9 and TIMP-1 and -2 were significantly higher than in controls while protein levels in cell supernatants and plasma did not differ between groups. The Center for Epidemiological Studies - Depression (CES-D) scale was used to assess depressive symptomatology. Repeated assessments during the first 18 months after MI showed significantly higher CES-D scores in patients compared with controls. However, there were no relationships between depressive mood and any of the measurements of MMP-9 or TIMPs. Conclusion: Our findings indicate that overexpression of MMP-9 and TIMPs in blood mononuclear cells and elevated depressive symptoms represent two unrelated phenomena after MI.

Place, publisher, year, edition, pages
Public Library of Science , 2014. Vol. 9, no 8, e105572- p.
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-110970DOI: 10.1371/journal.pone.0105572ISI: 000340952200062PubMedID: 25153995OAI: oai:DiVA.org:liu-110970DiVA: diva2:752000
Note

Funding Agencies|Swedish Research Council [521-2011-3847]; Swedish Heart-Lung Foundation [20120608]

Available from: 2014-10-02 Created: 2014-10-01 Last updated: 2017-12-05
In thesis
1. Leukocyte-derived matrix metalloproteinase-9 in patients with coronary artery disease: Associations with psychological stress and glucocorticoid sensitivity
Open this publication in new window or tab >>Leukocyte-derived matrix metalloproteinase-9 in patients with coronary artery disease: Associations with psychological stress and glucocorticoid sensitivity
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammation is closely associated with development of atherosclerosis. The proteolytic enzyme matrix metalloproteinase (MMP)-9 is considered to play a prominent role in this process. MMP-9 has also been introduced as a marker for plaque vulnerability. Still, the possible mechanisms behind altered levels of MMP-9 and its tissue inhibitors (TIMPs) in patients with atherosclerotic disease remain unclear. The general aim of this thesis was to compare leukocyte-derived MMP-9 and TIMPs in patients with coronary artery disease (CAD) and healthy controls and to further relate the findings to psychological stress and glucocorticoid sensitivity.

Levels of leukocyte-derived MMP-9 and TIMP-1 showed a significant difference between CAD patients and controls. Neutrophils in CAD patients were more prone to release MMP-9 and furthermore, PBMCs in patients expressed higher levels of MMP-9 and TIMP-1 and -2 mRNA than PBMCs in controls while there were no differences in plasma or serum levels. The increase in leukocyte-derived levels of MMP-9 and TIMPs indicate the presence of preactivated leukocytes in CAD.

Inflammation has been proposed as a mechanistic link between cardiovascular risk and depressive symptoms. We investigated whether the overexpression of leukocyte-derived MMP-9 and TIMPs in CAD patients was associated with psychological factors. Patients exhibited sustained elevations in depressive symptoms, however, these symptoms were not related to any MMP-9 or TIMP variables. The findings suggest that overexpression of leukocyte-derived MMP-9 and TIMPs and elevated depressive scores represent two parallel phenomena in CAD.

Chronic inflammation may be associated with reduced glucocorticoid sensitivity. We found that PBMCs in CAD patient expressed significantly increased levels of glucocorticoid receptor (GR)-α mRNA, whereas GR-β mRNA levels did not differ between patients and controls. Moreover, in ex vivo assays, dexamethasone efficiently suppressed MMP-9 and TIMPs equally or even more in patients compared to controls. The findings provide evidence for enhanced glucocorticoid sensitivity in CAD patients and also suggest that a state of relative hypocortisolism may contribute to the overexpression of leukocyte-derived MMP-9 and TIMPs.

Lastly, we explored the release of MMP-9, TIMPs and cortisol in response to acute mental stress in CAD patients. Patients who exhibited a significant stress-induced increase in serum MMP-9 also exhibited an altered cortisol response. Moreover, the susceptibility to stressinduced increase in serum MMP-9 was associated with shorter leukocyte telomere length and atherosclerotic plaque burden. The findings highlight the existence of a high-risk group which may be in need of improved diagnostic and therapeutic strategies.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1438
National Category
Cardiac and Cardiovascular Systems Immunology in the medical area Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114328 (URN)10.3384/diss.diva-114328 (DOI)978-91-7519-149-2 (ISBN)
Public defence
2015-03-20, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-02-18 Created: 2015-02-18 Last updated: 2015-02-18Bibliographically approved

Open Access in DiVA

fulltext(596 kB)125 downloads
File information
File name FULLTEXT01.pdfFile size 596 kBChecksum SHA-512
2a866d0e12235768af12a4a63d78175698287df33a1053c18fc26928d4d032c83cd0542d93251301b6a83a8683dddab62f0232a5c34c165017524e25076e3e4d
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Jönsson, SimonLundberg, AnnaJonasson, Lena

Search in DiVA

By author/editor
Jönsson, SimonLundberg, AnnaJonasson, Lena
By organisation
Division of Cardiovascular MedicineFaculty of Health SciencesDepartment of Cardiology in Linköping
In the same journal
PLoS ONE
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 125 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 159 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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