Statin Effects on Vascular Calcification Microarchitectural Changes in Aortic Calcium Deposits in Aged Hyperlipidemic Mice

Objective: Statins lower cardiovascular event risk, yet, they paradoxically increase coronary artery calcification, a marker consistently associated with increased cardiovascular risks. As calcium deposits influence rupture risk due to stress from compliance mismatch at their surfaces, we hypothesized that statins may lower cardiovascular risk by altering the microarchitecture of calcium deposits. Thus, using mice with preexisting vascular calcification, we tested whether pravastatin reduces the mineral surface area of calcium deposits. Approach and Results: Aged Apoe(-/-) mice were treated with pravastatin or vehicle for 20 weeks. Aortic calcification was assessed by in vivo micro-computed tomography/micro-positron emission tomography using fluorine-18-labeled sodium fluoride at weeks 0, 10, and 20 and by histomorphometry at euthanasia. Micro-computed tomography analysis showed that, in both groups, the amount of vascular calcification increased significantly over the 20-week period, but pravastatin treatment did not augment over the controls. In contrast, the micro-positron emission tomography analysis showed that, at week 10, the pravastatin group had less F-18 uptake, suggesting reduced surface area of actively mineralizing deposits, but this decrease was not sustained at week 20. However, a significant difference in the mineral deposit size was found by histomorphometry. The pravastatin group had significantly more aortic microcalcium deposits (<50 mu m in diameter) than the controls. The pravastatin group also had more vascular cells positive for alkaline phosphatase activity than the controls. The amount of collagen and osteopontin, additional osteoblastic markers, were not significantly different between the 2 groups. Conclusions: These results suggest that pravastatin treatment alters the microarchitecture of aortic calcium deposits with potential effects on plaque stability.

Automated summary

The study suggests that pravastatin treatment alters the microarchitecture of aortic calcium deposits, potentially impacting plaque stability.