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Inflammation, Plaque Vulnerability and Cardiovascular Risk

Grufman, Helena LU (2015) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2015:74.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Docent Bäck, Magnus, Center för Molekylärmedicin, Karolinska Institutet, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Atherosclerosis, carotid plaque, acute coronary syndrome, CRP, cytokines, aging, IL-27
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2015:74
pages
71 pages
publisher
Exp Cardiovascular Research Unit, Department of Clinical Sciences, Malmö
defense location
CRC 2 (CRC 93-09-002a), Jan Waldenströms gata 35, SUS Malmö
defense date
2015-06-13 09:00
ISSN
1652-8220
ISBN
978-91-7619-153-8
language
English
LU publication?
yes
id
0ac1a5c5-bb4f-4c0e-b930-7ff22e279ad6 (old id 5425808)
date added to LUP
2015-05-26 07:56:23
date last changed
2016-09-19 08:44:48
@phdthesis{0ac1a5c5-bb4f-4c0e-b930-7ff22e279ad6,
  abstract     = {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.},
  author       = {Grufman, Helena},
  isbn         = {978-91-7619-153-8},
  issn         = {1652-8220},
  keyword      = {Atherosclerosis,carotid plaque,acute coronary syndrome,CRP,cytokines,aging,IL-27},
  language     = {eng},
  pages        = {71},
  publisher    = {Exp Cardiovascular Research Unit, Department of Clinical Sciences, Malmö},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Inflammation, Plaque Vulnerability and Cardiovascular Risk},
  volume       = {2015:74},
  year         = {2015},
}