OBJECTIVE Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification, as detected by fluorine-18-sodium fluoride, has recently been recognized as a valuable indicator in predicting atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification involved in the pathogenesis of AAA remains elusive. Approach and Results: Microcalcification was analyzed in human aneurysmal aortas histologically and in AngII (angiotensin II)-infused ApoE-/- mouse aortas by fluorine-18-sodium fluoride positron emission tomography and X-ray computed tomography scanning in chronological order in live animals. AAA patients' aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared with non-AAA patients. Enhanced fluorine-18-sodium fluoride uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo. RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII-infused ApoE-/- mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 (runt-related transcription factor 2) in AAA. Consistently, vascular smooth muscle cell-specific Runx2 deficiency markedly repressed AngII-induced AAA formation in the ApoE-/- mice compared with the control littermates. CONCLUSIONS Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment.

中文翻译：

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Runx2（与Runt相关的转录因子2）介导的微钙化是腹部主动脉瘤的一种新型病理特征和潜在介体。

目的腹主动脉瘤（AAAs）是高度致死性疾病，没有有效的临床预测指标和治疗靶标。氟18氟化钠检测到的血管微钙化最近被认为是预测动脉粥样硬化斑块破裂和AAA扩张的重要指标。但是，血管微钙化是否参与AAA的发病机制仍不清楚。方法和结果：通过活体动物中的氟18-氟化钠正电子发射断层扫描和X射线计算机断层扫描按时间顺序对人动脉瘤主动脉和注入AngII（血管紧张素II）的ApoE-/-小鼠主动脉进行了微钙化分析。 。AAA患者 与非AAA患者相比，主动脉组织在弹性纤维降解附近区域的主动脉介质中显示出明显增强的微钙化。小鼠体内主动脉扩张之前，氟18-氟化钠吸收增加。AngII输注第7天的微钙化阳性小鼠在随后的14至28天显示出主动脉急剧扩张，而AngII输注的微钙化阴性小鼠和生理盐水诱导的小鼠则没有AAA。微钙化的主要成分羟基磷灰石的应用加剧了AngII诱导的AAA在体内的形成。输注4天AngII的ApoE-/-小鼠肾上主动脉的RNA测序分析和ChIP-Atlas数据库进行的生物信息学分析确定了成骨转录因子Runx2（与runt相关的转录因子2）可能参与了AAA。一致地，与同窝同窝幼仔相比，血管平滑肌细胞特异的Runx2缺陷明显抑制了ApoE-/-小鼠中AngII诱导的AAA形成。结论我们的研究表明微钙化是AAA的一种新型病理特征和潜在的介质，而靶向微钙化可能代表AAA预防和治疗的有前途的策略。