Cardiovascular Effects of Early and Postponed Statin Treatment After Ovariectomy in Prediabetic Rat

We investigated the effects of early and postponed statin therapy after ovariectomy on the cardiovascular system in an experimental model of insulin resistance (hereditary hypertriglyceridemic rats). Thirty hereditary hypertriglyceridemic rats were ovariectomized at 9 weeks of age. Two groups received atorvastatin (5 mg/kg) from the 2nd (early statin) or 14th (postponed statin) week after ovariectomy; the control group received no therapy. Arterial strain was measured by duplex ultrasound at week 21 post ovariectomy. The experiment was terminated at week 22, when the expression of vascular genes was measured together with metabolic and inflammatory parameters associated with the cardiovascular system. Atorvastatin treatment had no positive effect on arterial strain and caused mixed metabolic changes including increased content of triglycerides in striated muscles, and decreased serum levels of monocyte chemoattractant protein-1, fasting glycemia, serum triglycerides and non-esterified fatty acids. The postponed statin group exhibited significantly higher endothelial nitric oxide synthase (eNOS) expression in the myocardium compared to the early statin group, whereas aortic expression was lower in both groups and serum interleukin 6 was moderately decreased. Neither early nor postponed statin therapy improved arterial strain. Early/prolonged atorvastatin treatment was associated with decreased aortic eNOS expression and increased muscle triglyceride content. Postponed/shorter treatment increased myocardial eNOS expression but decreased connexin-43. These findings suggest that in a metabolically impaired state, the timing and duration of statin therapy can result in complex and opposing organ-specific effects.