Chronic inflammation is recognized as a major driving force in atherogenesis, yet the factors which trigger and sustain the inflammatory reaction in arterial wall are largely unknown. On the other hand we know that the risk of atherosclerosis is greatly increased in chronic inflammatory diseases such as rheumatoid arthritis (RA). In RA the risk of cardiovascular diseases is increased by 2-3 fold and is of the same magnitude as in type 2 diabetes. It is however, not known how the presence of systemic inflammation increases the risk of atherosclerosis. The aim of the research group is to identify factors which could trigger the inflammation in the arterial wall and to elucidate the factors which mediate the increased risk of atherosclerosis in chronic inflammatory diseases, RA in particular.

We have identified several novel factors which are capable of triggering inflammatory reaction in arterial wall. Cholesterol crystals are a common constituent of atherosclerotic lesions already early in the process of atherogenesis. We have studied their possible significance in the pathogenesis of athersoclerosis. One of the main findigs was that cholesterol crystals are strong activators of the inflammasome signalling cascade which results in production of highly proinflammatory interleukin-1 (IL-1) beta (Rajamaki et al 2010). Cholesterol crystals may thus represent an important link between lipid metabolism and inflammation.

In chronic inflammation, and in inflammatory diseases, the levels of acute phase protein serum amyloid A (SAA), are increased up to 1000 fold. We hypothesize that SAA is one of the key factors which mediate the increased risk of atherosclerosis in inflammatory diseases. We have shown that SAA alone is capable of activating the so called inflammasome signalling cascade which results in generation of mature proinflammatory IL-1beta (Niemi et al 2011). We currently study the role of SAA in immune system activation, and the regulation of the effects of SAA by lipoproteins.

Currently the treatment of atherosclerosis has been focused on decreasing the levels of blood lipids and there are no drugs which would solely target the inflammation in atherosclerosis. Thus one of the important aims of the project is to identify suitable targets for the novel anti-inflammatory therapies to treat atherosclerosis.

Selected publications

Niemi K, Teirilä L, Lappalainen J, Rajamäki K, Baumann MH, Öörni K, Wolff H, Kovanen PT, Matikainen S, Eklund KK. Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway. J Immunol. 2011;186:6119-28.

Rajamäki K, Lappalainen J, Öörni K, Välimäki E, Matikainen S, Kovanen PT, Eklund KK. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One. 2010;5:e11765.