Adaptive Immunity in Cardiovascular Disease

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.

Grantor dc:publisher

Department of Clinical Sciences, Lund University

Year dc:date

2013

Author dc:creator

• Engelbertsen, Daniel

• Clinical Medicine

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

urn:isbn:978-91-87449-21-5

OAI identifier oai:identifier

oai:lup.lub.lu.se:1cdf5a85-7184-4d6d-ab5a-e79eece2cc1d