Blood flow sensor susceptibility to lipoproteins in early arteriosclerosis and its clinical improvement by statin therapy — a nanoplaque study

Utilizing the isolated blood flow sensor syndecan (heparan/chondroitin sulfate proteoglycan, HS/CS-PG) from arterial endothelium and smooth muscle cell membranes and coating therewith a silica surface, we were able to observe the very earliest stages of arteriosclerotic plaque development, the so-called nanoplaque build-up, by ellipsometric techniques (patent EP 0 946 876). The arteriosclerotic nanoplaque is represented by the ternary aggregational complex of the HS-PG receptor (identical with the blood flow sensor), lipoprotein particles and calcium ions. The model was validated in several clinical studies on cardiovascular high-risk patients applying their blood lipoprotein fractions and, among others, proved the inhibiting effect of statins on nanoplaque formation. On the other hand, we could directly demonstrate the nanoplaque build-up in isolated, explanted human coronary arteries from heart transplantations on their endothelial cell membranes and thus quantify the influence of lipoprotein and certain isoforms thereof on the signal transduction cascade evoked from these membranes. For example, binding of LDL (low-density lipoprotein) to the HS-PG blood flow sensor and forming an arteriosclerotic nanoplaque induces cell membrane depolarization, vasoconstriction and lowering of second messenger cyclic nucleotides. These processes in a biomembrane have immediate relevance for the formation of arteriosclerotic plaques as well as their therapy in patients.