Prevention of atherosclerosis

The first step in the development of atherosclerosis is the retention of LDL in the arterial wall. This process occurs when LDL binds to proteoglycans in the extracellular matrix, primarily biglycan. The aim of the present project is to interrupt this interaction, thus keeping LDL in the circulation and avoiding the chronic inflammation characteristic for atherosclerosis.

We apply a two-pronged approach. The first is to find a small molecule that interferes with LDL-biglycan binding. This entails screening of small molecule libraries and further testing of ‘hits’ in an in vitro model.

The second, which emerged in 2020, is to apply CRISPR technology to modify apoB produced by liver cells. A single change in the nucleotide sequence can reduce LDL’s affinity for proteoglycans in the arterial wall, without compromising its normal function. The vector for the CRISPR components is modified HDL.

The study is still active in 2021.

Primary Investigator: Martin Heier

Co-investigators/participants:
Svein Olav Kolset
Knut Dahl-Jørgensen

External collaborators:
Alexandra Gade
Michael N. Oda
Magnar Bjørås