Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patients.
Coating a silica surface with the isolated lipoprotein receptor proteoheparan sulfate (HS-PG) from arterial endothelium and vascular matrices and adding both the atherogenic VLDL/IDL/LDL lipid fraction in its native composition and Ca(2+) ions, we could observe in vitro the earliest stages of atherosclerotic plaque development by ellipsometric techniques (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. In eight patients who had undergone an aortocoronary bypass operation, the reduction of atherosclerotic nanoplaque formation amounted to 11.9+/-2.5% (p<0.0078) and of nanoplaque size to 24.4+/-8.1% (p<0.0234), respectively, after a 2-month therapy with Ginkgo biloba extract (2x 120 mg daily, EGb 761). Additionally, superoxide dismutase (SOD) activity was upregulated by 15.7+/-7.0% (p<0.0391), the quotient oxLDL/LDL lowered by 17.0+/-5.5% (p<0.0234) and lipoprotein(a) concentration decreased by 23.4+/-7.9% (p<0.0234) in the patients' blood. The concentration of the vasodilating substances cAMP and cGMP was augmented by 37.5+/-9.1% (p<0.0078) and 27.7+/-8.3% (p<0.0156), respectively. A multiple regression analysis between the patients' VLDL/IDL/LDL lipoprotein fraction applied in the ellipsometry measurements as well as the further risk factors oxLDL/LDL and Lp(a) on the one hand and changes in nanoplaque formation on the other hand reveals a basis for a mechanistic explanation of nanoplaque reduction under ginkgo treatment. The atherosclerosis inhibiting effect is possibly due to an upregulation in the body's own radical scavenging enzymes and an attenuation of the risk factors oxLDL/LDL and Lp(a).
Rodríguez
M
M
Charité, Campus Benjamin Franklin, Institute of Physiology, Berlin, Germany.
Ringstad
L
L
Schäfer
P
P
Just
S
S
Hofer
H W
HW
Malmsten
M
M
Siegel
G
G
D000327:Adsorption; D000368:Aged; D050197:Atherosclerosis / Q000473:pathology* / Q000517:prevention & control*; D015374:Biosensing Techniques; D001026:Coronary Artery Bypass; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D020441:Ginkgo biloba; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010936:Plant Extracts / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000097:blood; D000096983:Ginkgo Extract
D000242:Cyclic AMP; D006152:Cyclic GMP; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D010936:Plant Extracts; D013482:Superoxide Dismutase; C099252:oxidized low density lipoprotein; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract