Statin Effects on Vascular Calcification: Microarchitectural Changes in Aortic Calcium Deposits in Aged Hyperlipidemic Mice.
Statin Effects on Vascular Calcification: Microarchitectural Changes in Aortic Calcium Deposits in Aged Hyperlipidemic Mice.
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DOI：
10.1161/atvbaha.120.315737
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Tintut Y
中科院分区：
文献类型：
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作者：
Xian JZ;Lu M;Fong F;Qiao R;Patel NR;Abeydeera D;Iriana S;Demer LL;Tintut Y
他汀类药物降低了心血管事件的风险，但却矛盾地增加了冠状动脉钙化，这是一个始终与心血管风险增加相关的标志物。由于钙沉积物表面的顺应性不匹配会影响破裂风险，我们假设他汀类药物可能通过改变钙沉积物的微结构来降低心血管风险。因此，我们使用先前存在血管钙化的小鼠，测试普伐他汀是否减少钙沉积物的矿物表面积。老龄Apoe−/−小鼠给予普伐他汀或对照药治疗20周。在第0周、第10周和第20周采用体内18F-NaF-μPET/μCT成像和安乐死时采用组织形态测量法评估主动脉钙化情况。MicroCT分析显示，在两组中，血管钙化的数量在20周内显著增加，但普伐他汀治疗并没有比对照组增加。相比之下，μPET分析显示，在第10周，普伐他汀组的18F摄取减少，表明活跃矿化矿床的表面积减少，但这种减少在第20周没有持续。然而，通过组织形态计量学发现矿床大小有显著差异。普伐他汀组的主动脉微钙沉积（直径< 50 μm）明显多于对照组。普伐他汀组也比对照组有更多的血管细胞呈碱性磷酸酶活性阳性。胶原蛋白和骨桥蛋白（另一种成骨细胞标志物）的数量在两组之间无显著差异。这些结果表明，普伐他汀治疗改变了主动脉钙沉积的微结构，对斑块稳定性有潜在影响。
Statins lower cardiovascular event risk, yet they paradoxically increase coronary artery calcification, a marker consistently associated with increased cardiovascular risks. Since 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 pre-existing vascular calcification, we tested whether pravastatin reduces the mineral surface area of calcium deposits. Aged Apoe−/− mice were treated with pravastatin or vehicle for 20 weeks. Aortic calcification was assessed by in vivo 18F-NaF-μPET/μCT imaging at weeks 0, 10 and 20 and by histomorphometry at euthanasia. MicroCT 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 μPET analysis showed that, at week 10, the pravastatin group had less 18F 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 μm 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 two groups. These results suggest that pravastatin treatment alters the microarchitecture of aortic calcium deposits with potential effects on plaque stability.