Reduction of arteriosclerotic nanoplaque formation and size by n-3 fatty acids in patients after valvular defect operation.
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.
Koppe
Cordelia
C
Institute of Physiology, Charité, Campus Benjamin Franklin, Berlin, Germany.
Rodríguez
Miguel
M
Winkler
Karl
K
Pietzsch
Jens
J
Neumann
Konrad
K
Hiemann
Nicola E
NE
Hetzer
Roland
R
Malmsten
Martin
M
Siegel
Günter
G
D000368:Aged; D001161:Arteriosclerosis / Q000473:pathology* / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006349:Heart Valve Diseases / Q000473:pathology / Q000601:surgery*; D006351:Heart Valves / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D036103:Nanotechnology
D015525:Fatty Acids, Omega-3; D008055:Lipids; D008074:Lipoproteins; D002118:Calcium