Reduction of Arteriosclerotic Nanoplaque Formation and Size by n-3 Fatty Acids in Patients after Valvular Defect Operation

Abstract

Background/Methods: Coating a silica surface with the isolated lipoprotein receptor heparan sulfate proteoglycan (HS-PG) from arterial endothelium and vascular matrices, we could observe the very earliest stages of arteriosclerotic plaque development by ellipsometric techniques in vitro (patent EP 0 946 876). This so-called nanoplaque formation is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies on statins in cardiovascular high-risk patients applying their native blood lipoprotein fractions. Results: In 7 patients who had undergone a valvular defect operation, the reduction of arteriosclerotic nanoplaque formation in normal Krebs solution amounted to 6.1 ± 2.3% (p < 0.0156) and of nanoplaque size to 37.5 ± 13.2% (p < 0.0312), respectively, after a 3-month therapy with n-3 fatty acids (3 ··3 g daily, Ameu® 500 mg). Additionally, the quotient oxLDL/LDL was lowered by 6.8 ± 2.1% (p < 0.0166), the MDA concentration remained unchanged and the lipoprotein(a) concentration decreased by 15.8 ± 5.6% (p < 0.0469) in the patients’ blood. The concentration of the nanoplaque promoting particles VLDL and total triglycerides was diminished by 34.1 ± 11.6% (p < 0.0469) and 26.7 ± 10.8% (p < 0.0156), respectively. Furthermore, the ratio of the strongly atherogenic small dense to the total LDL cholesterol (LDL5+LDL6)/LDLtot decreased by 9.9 ± 3.0% (p < 0.0174). Conclusions: A combinatorial regression analysis revealed a basis for a mechanistic explanation of nanoplaque reduction under n-3 fatty acid treatment. This effect was possibly due to the beneficial changes in lipid concentrations and an attenuation of the risk factors oxLDL/LDL and (LDL5+LDL6)/LDLtot.