Atheroprotective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats

Abstract

Background: The present work explores the myriad of biochemical and cellular changes that are featured in the early stages of atherosclerosis; if unchecked these changes lead to the complicated atherosclerotic plaque formation. The influence of a low-molecular-weight heparin derivative on the aortic aberrations and lipoprotein oxidation has been assessed in an experimental model of hypercholesterolemic atherogenesis.

Methods: Two groups of male Wistar rats (140+/-10 g) were fed a hypercholesterolemic atherogenic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil; CCT diet) for 2 weeks; one of these groups received LMWH (Certoparin) treatment of 300 microg/day/rat, s.c. for 7 days. An untreated control and a LMWH drug control group were also included.

Results: Abnormal increase in the aortic lipids -glycosaminoglycans levels (p<0.001) in CCT-diet fed group was circumvented by the exogenous glycosaminoglycan (LMWH) treatment (p<0.001). The escalation of oxidative stress (markers-lipid peroxidation and thiol levels, superoxide dismutase and catalase activities) in the atherogenic aorta was minimised by LMWH treatment. Further, an increased susceptibility of the apo B-containing lipoproteins (LDL+VLDL) to oxidation in vitro, induced by copper ions and Fenton's reagent, was observed in the untreated CCT diet fed group. This paper reports the favorable modulation of these oxidative changes by LMWH administration. Vascular protection by LMWH is further substantiated by the normal aortic histologic findings as against the appearance of foam cells in the untreated atherogenic group.

Conclusion: The exogenous heparin-derivative (LMWH) treatment attempted in this experimental model of hypercholesterolemic atherogenesis affords substantial protection against abnormal levels of aortic lipids and glycosaminoglycans, aortic oxidative stress and also stunts the lipoprotein peroxidative process, thereby proving its multi-faceted anti-atherogenic effects.