Modification of low density lipoprotein (LDL) particles and their interaction with the molecules of the extracellular matrix and foam cell formation are key processes in the development of the atherosclerotic lesions. In our studies, we have examined the effects of various lipases (phospholipase A2 and sphingomyelinase) and proteases (mast cell proteases and cathepsins) on LDL particles. These modifications lead to aggregation and fusion of LDL, enhance the binding of LDL to human aortic proteoglycans and induce foam cell formation. Since the extracellular pH in atherosclerotic lesions can decrease locally and so generate microdomains having an acidic pH, we have recently also examined the effect of pH on these processes. Based on our present results, it appears that all these key processes of atherosclerosis are enhanced at acidic pH.

In our current projects, we apply lipidomics to study the individual differences in LDL modification. We are also isolating extracellular lipoprotein particles from human atherosclerotic arteries and stenotic aortic valves to be able to identify the lipoprotein modifications that occur during the development of atherosclerosis and aortic stenosis.

Selected publications

Plihtari R, Kovanen PT, Öörni K. Acidity increases the uptake of native LDL by human monocyte-derived macrophages. Atherosclerosis. 2011; Apr. 22 [epub ahead of print]

Plihtari R, Hurt-Camejo E, Öörni K, Kovanen PT. Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase. J Lipid Res. 2010;51:1801-9.

Öörni K, Kovanen PT. Lipoprotein modification by secretory phospholipase A(2) enzymes contributes to the initiation and progression of atherosclerosis. Curr Opin Lipidol. 2009;20:421-7.

Lähdesmäki K, Plihtari R, Soininen P, Hurt-Camejo E, Ala-Korpela M, Öörni K, Kovanen PT. Phospholipase A(2)-modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH. Atherosclerosis. 2009;207:352-9.

Öörni K, Kovanen PT. Enhanced extracellular lipid accumulation in acidic environment. Curr Opin Lipidol. 2006;17:534-40.

Öörni K, Pentikäinen MO, Ala-Korpela M, Kovanen PT. Aggregation, fusion, and vesicle formation of modified LDL particles: molecular mechanisms and effects on matrix interaction. J Lipid Res. 2000;41:1703-14.