Effect of gemfibrozil on peripheral atherosclerosis and platelet activation in a pig model of hyperlipidemia.
BACKGROUND
Gemfibrozil has been shown to have beneficial effects in the primary and secondary prevention of atherosclerosis. However, a platelet pro-activating effect induced by the drug has been reported.


METHODS
We analysed the effect of hyperlipidemia and its treatment with gemfibrozil on platelet-fibrinogen binding and the development of early fibrinogen-rich vascular lesions in a porcine model of atherosclerosis. Polyclonal antibodies were raised against purified pig fibrinogen and intact platelets. Two groups of animals were fed a cholesterol/saturated fat-enriched diet for 50 days; one group was treated with gemfibrozil and the other with placebo.


RESULTS
The hyperlipidemic diet induced a significant increase in total cholesterol; this was prevented by gemfibrozil (P<0.05). The increase in platelet-fibrinogen binding induced by hypercholesterolemia was mildly reduced in the gemfibrozil treated animals. Histological analysis of aortic vascular wall (abdominal aorta at the iliac bifurcation) from hyperlipidemic animals showed early lesions with fibrinogen infiltration; the lesions were reduced in the fibrate-treated animals.


CONCLUSIONS
Gemfibrozil delayed the development of peripheral atherosclerotic plaque, normalised the impaired lipid profile induced by the hyperlipidemic diet and did not show a functionally detectable platelet pro-activating effect able to increase platelet-fibrinogen binding.
Royo
T
T
Cardiovascular Research Centre, IIBB/CSIC-Hospital de la Santa Creu i, Sant Pau-UAB, Spain.
Alfón
J
J
Berrozpe
M
M
Badimon
L
L
D000818:Animals; D000906:Antibodies; D001012:Aorta, Abdominal / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015248:Gemfibrozil / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000473:pathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D010919:Placebos; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D013552:Swine
D000906:Antibodies; D000960:Hypolipidemic Agents; D010919:Placebos; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; D002784:Cholesterol; D015248:Gemfibrozil