Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian...

Area of Science:

• Cardiovascular Science
• Endocrinology
• Pharmacology

Background:

• Menopause alters blood lipoprotein composition, potentially affecting hypolipidemic therapy efficacy.
• Surgical menopause in female hamsters on a hypercholesterolemic diet serves as a model to study these effects.

Purpose of the Study:

• To investigate the impact of surgical menopause on serum lipids and atherosclerosis.
• To evaluate the effectiveness of simvastatin treatment, both immediate and delayed, on lipid profiles and atherosclerotic changes post-menopause.

Main Methods:

• Female golden Syrian hamsters were ovariectomized or sham-operated and fed a hypercholesterolemic diet for 12 weeks.
• Simvastatin (10 mg/kg) was administered either immediately or 4 weeks post-ovariectomy.
• Atherosclerotic changes were assessed in the aorta using stereomicroscopy; serum lipids were analyzed.

Main Results:

• Ovariectomized animals exhibited a tenfold increase in LDL triglycerides and higher atherosclerosis prevalence compared to controls.
• Simvastatin treatment significantly reduced atherosclerosis but did not alter individual serum lipids like LDL cholesterol.
• Treatment improved lipid profiles by increasing HDL cholesterol, with no significant difference between immediate and delayed administration.

Conclusions:

• Surgical menopause induces hypertriglyceridemia and promotes atherosclerosis, partly mediated by alterations in lipoprotein metabolism.
• Simvastatin effectively mitigates post-menopausal atherosclerosis, primarily through increasing HDL cholesterol rather than decreasing LDL cholesterol.
• The timing of simvastatin initiation did not significantly impact its therapeutic efficacy in this model.