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Inflammation, Plaque Vulnerability and Cardiovascular Risk

På svenska

Author

  • Helena Grufman

Summary, in English

Acute cardiovascular events, most commonly caused by rupture of an atherosclerotic plaque, lie behind one third of all deaths worldwide. Atherosclerosis is an inflammatory disease of large and medium sized arteries driven by retention of lipid in the arterial wall. Inflammatory activity in the plaque is believed to be an important driving force behind plaque progression and rupture. However it is not known how well inflammatory markers measured in blood correlate with plaque inflammation. We correlated plasma levels of hsCRP with the content of macrophages, IL-6, IL-10, TNF-α and MCP-1 in carotid plaques removed by endarterectomy not finding any association, which suggests that hsCRP is a marker of systemic inflammation, not plaque inflammation. In our next study we found that plasma levels of fractalkine, MIP-1β and TNF-α correlated with levels of the same cytokines in carotid endarterectomy specimens indicating that these markers could be used to measure plaque inflammation. We also found that plasma levels in the upper tertile of these markers were associated with a higher risk of future transitory ischemic attacks. Thirdly, we compared histological features and levels of inflammatory markers in endarterectomy specimens from elderly patients (≥70 years) with those from younger patients. We found that elderly symptomatic patients had the highest plaque levels of lipids and macrophages. Plaques from elderly patients had lower levels of inflammatory cytokines and elastin than younger patients, suggesting that plaque vulnerability in elderly is not associated with increased inflammatory activity in plaques but possibly with decreased lipid clearance and impaired tissue repair. IL-27 is a cytokine that has recently been shown to protect mice from atherosclerosis but is elevated in plasma of humans with atherosclerotic disease. In our last study we found that elevated levels of IL-27 in plasma from patients with acute coronary syndrome predict future myocardial infarction or cardiovascular death after a median follow-up of 2.2 years.

Publishing year

2015

Language

English

Publication/Series

Lund University Faculty of Medicine Doctoral Dissertation Series

Volume

2015:74

Document type

Dissertation

Publisher

Exp Cardiovascular Research Unit, Department of Clinical Sciences, Malmö

Topic

  • Clinical Medicine

Keywords

  • Atherosclerosis
  • carotid plaque
  • acute coronary syndrome
  • CRP
  • cytokines
  • aging
  • IL-27

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-7619-153-8

Defence date

13 June 2015

Defence time

09:00

Defence place

CRC 2 (CRC 93-09-002a), Jan Waldenströms gata 35, SUS Malmö

Opponent

  • Magnus Bäck (Docent)