Atherogenesis and plaque rupture, surface/interface-related phenomena

Abstract

In atherogenesis, free oxygen radicals cause a lipid peroxidation of apoB100-containing lipoproteins in the blood, at the blood–endothelium-interface and in the subendothelial space. These lipoproteins easily aggregate, bind to their receptor heparan sulfate proteoglycan and calcify to arteriosclerotic nanoplaques (ternary complexes). Nanoplaque formation was measured by ellipsometry, both in vitro on an HS-PG coated hydrophobic silica surface and also in vivo on living human coronary endothelial cells, which had overgrown the silica surface. Reversely, we show with the same techniques that, in dependence on the degree of peroxidation and epitope in concern, oxLDL attacks its molecular receptor and thus can induce degradation of arteriosclerotic plaques and, in a combined action with inflammatory processes, even a plaque rupture.In a previous work, we had found PML-NB, fibrous cap (collagens, proteoglycans) and HSBGF binding sites (e.g., TGFβ1) up-regulated and NFκB down-regulated. With this background knowledge we created a molecular feedback control circuit model where PML-NB functions as regulation centre, fibrous cap as controlled variable, HSBGF binding sites as receptor and NFκB as effector. Since NFκB is inhibited by one reaction strand in this model and inhibits itself collagen and proteoglycan synthesis in the fibrous cap of the plaque, this double check (disinhibition) causes a stabilization of the fibrous cap through a specially strong collagen and proteoglycan production, which in addition is supported by circulating TGFβ. TGFβ furthers also calcification, so that fibrous cap tensile strength and resistance to shear stress are imparted. This way, a plaque rupture may possibly be averted.