The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Andreas Edsfeltdt

Andreas Edsfeldt

Associate professor

Andreas Edsfeltdt

Detecting the Vulnerable Plaque


  • Andreas Edsfeldt

Summary, in English

Myocardial infarction and stroke, mainly caused by a rupture of an atherosclerotic plaque, are two of the most

common causes of mortality and morbidity in the world. Previous studies have pointed out inflammation, driven

by inflammatory lipids, as the keystone in the formation of the rupture prone vulnerable plaque. The risk for a

plaque rupture is greatly enhanced in the diabetic population and increased inflammation has been suggested as the

contributing factor. However, the mechanism remains unknown. One of the current greatest challenges in the

atherosclerotic field is to identify subjects with plaques that are vulnerable before the occurrence of a plaque


In this thesis we provide evidence that the enzyme lipoprotein associated phospholipase A2 (LpPLA2) and the

lipids lysophosphatidylcholines and sphingolipids (ceramides, lactosylceramides, glucosylceramides) contribute to

the inflammatory process and that they are associated with the vulnerable plaque. This suggests that the synthesis

of these lipids may be possible therapeutic targets. We also show that the inflammatory process in the plaque is

reflected in the peripheral blood, as measured by cytokines, whereas no association was found for soluble

urokinase-type plasminogen activator receptor. The inflammatory cytokines MIP-1β, TNF-α and fractalkine

predict the inflammatory plaque with high sensitivity and specificity, proposing that these inflammatory cytokines

could be used as plasma markers for plaque inflammation. Finally, we provide novel data regarding the biology of

the diabetic plaque. According to our data the inflammatory activity is not increased in the diabetic plaque tissue.

Diabetic plaques contained less stabilizing extracellular matrix proteins (collagen and elastin). Additionally the

plaque levels of the inflammation regulating cytokine IL-10 and the growth factor platelet derived growth factor

as well as the smooth muscle cell stimulating matrix metalloproteinase 2 were significantly decreased in diabetic

plaque tissue. These findings were independent of the presence of symptoms.

In summary, this thesis shows that lipids as LysoPCs and glycosphingolipids are important inducers of plaque

inflammation and may be possible therapeutic targets. In the general population the inflammatory activity is an

important factor for the formation of a vulnerable plaque and this inflammatory process is reflected in blood,

hinting a role for fractalkine, MIP-1β and TNF-α as future biomarkers. In the diabetic population, however, an

impaired tissue repair mechanism seems to be the keystone of plaque vulnerability, rather than inflammation,

emphasizing the need for new therapeutic approaches for diabetics.


  • Cardiovascular Research - Immunity and Atherosclerosis
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year





Lund University Faculty of Medicine Doctoral Dissertation Series



Document type



Experimental Cardiovascular Research Unit, Lund University


  • Cardiac and Cardiovascular Systems


  • Atherosclerosis
  • Carotid plaque
  • Inflammation
  • Diabetes
  • LpPLA2
  • suPAR
  • Cytokines
  • Lipids



Research group

  • Cardiovascular Research - Immunity and Atherosclerosis


  • Isabel Goncalves
  • Jan Nilsson


  • ISSN: 1652-8220
  • ISBN: 978-91-87449-89-5

Defence date

15 November 2013

Defence time


Defence place

Föreläsningssalen på Kvinnokliniken, Jan Waldenströmsgata 47, ingång 74, Skånes Universitetssjukhus i Malmö


  • Gerard Pasterkamp (MD, PhD)