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Daniel Engelbertsen

Assistant researcher

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Adaptive Immunity in Cardiovascular Disease

Author

  • Daniel Engelbertsen

Summary, in English

Atherosclerosis, thickening of the major arteries, is a chronic disease leading to cardiovascular disease (CVD) such as myocardial infarction (MI) and stroke, both affecting millions worldwide. T-cells and antibodies have been implicated in atherosclerosis. This thesis contains studies on CD4+ helper subsets and studies on antibodies against methylglyoxal-modified apolipoprotein B100 (MGO-ApoB100).

In the prospective Malmö Diet and Cancer cohort we studied the relation of T helper 1 (Th1) and T helper 2 (Th2) cells to future cardiovacular events. We found that baseline-levels of Th2 cells, but not Th1 cells, were inversely associated with intima-media thickness in the cohort and future coronary events in women. In another cohort, the SUMMIT cohort, we found that type 2 diabetes patients with concomitant CVD were characterized by elevated levels of pro-inflammatory CD4+ T effector memory cells. Using a novel technique (the matrigel) for determining the immune responses in vivo, Th2 responses against human ApoB100 was characterized. In another study, genetic deletion of the signaling protein myeloid differentiation protein 88 (MyD88) in CD4+ T cells was found to reduce atherosclerosis. This reduction was associated with decreased production of the pro-inflammatory cytokine IL-17. In two separate studies, IgM antibodies against MGO-ApoB or MGO-ApoB-peptides were observed to be associated with reduced CVD. The mechanism mediating this protection against CVD remains to be clarified.

This thesis presents and discusses aspects of immunity, which are interesting targets for pharmaceutical intervention. Various components of adaptive immunity may be useful as biomarkers for determining patients with increased risk of developing CVD.

Department/s

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

Publishing year

2013

Language

English

Publication/Series

Lund University Faculty of Medicine Doctoral Dissertation Series

Volume

2013:51

Document type

Dissertation

Publisher

Department of Clinical Sciences, Lund University

Topic

  • Clinical Medicine

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

Supervisor

  • Eva Bengtsson
  • Jan Nilsson
  • Harry Björkbacka

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-87449-21-5

Defence date

17 May 2013

Defence time

09:00

Defence place

Kvinnoklinikens Aula, Jan Waldenströms gata 47 , SUS Malmö

Opponent

  • Andrew Lichtman (Professor)