Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart.
Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart.
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遗传谱系追踪揭示了动脉生成是小鼠心脏侧枝生长的主要机制
DOI：
10.1093/cvr/cvw005
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发表时间：
2016-03-01
影响因子：
10.8
通讯作者：
Zhou B
中科院分区：
文献类型：
--
作者：
He L;Liu Q;Hu T;Huang X;Zhang H;Tian X;Yan Y;Wang L;Huang Y;Miquerol L;Wythe JD;Zhou B
毛细血管和动脉内皮细胞在新生儿和成人心脏中具有许多共同的分子标记。在这里，我们的目标是建立一个遗传工具，区分这两种类型的血管，以确定侧支动脉形成的细胞机制。使用Apln-GFP和Apln-LacZ报告小鼠，我们证明了APLN表达富集在冠状动脉血管内皮细胞中。然而，APLN表达在冠状动脉内皮细胞中减少。使用Apln-CreER小鼠系进行遗传谱系追踪，稳健标记毛细血管内皮细胞，但不标记动脉内皮细胞。我们利用Apln-CreER的这种差异活性来研究心肌梗死（MI）后的侧支动脉形成。在新生儿心脏MI模型中，我们发现Apln-CreER标记的毛细血管内皮细胞对大的侧支动脉没有贡献。相反，这些大的侧支动脉主要来自预先存在的、很少标记的冠状动脉，指示动脉生成。此外，在成人心脏MI模型中，Apln-CreER活性还将大直径动脉和小直径动脉与毛细血管区分开。在这种情况下的谱系追踪表明，在梗死心肌和边缘区域的大多数大小冠状动脉不是来自毛细血管，而是来自预先存在的动脉。Apln-CreER介导的谱系示踪区分新生儿和成人心脏中的毛细血管和大动脉。通过基因定位，我们证明了预先存在的动脉，而不是毛细血管，广泛地促进了心肌损伤后侧支动脉的形成。这些结果表明，动脉生成是侧支血管形成的主要机制。
Capillary and arterial endothelial cells share many common molecular markers in both the neonatal and adult hearts. Herein, we aim to establish a genetic tool that distinguishes these two types of vessels in order to determine the cellular mechanism underlying collateral artery formation. Using Apln-GFP and Apln-LacZ reporter mice, we demonstrate that APLN expression is enriched in coronary vascular endothelial cells. However, APLN expression is reduced in coronary arterial endothelial cells. Genetic lineage tracing, using an Apln-CreER mouse line, robustly labelled capillary endothelial cells, but not arterial endothelial cells. We leveraged this differential activity of Apln-CreER to study collateral artery formation following myocardial infarction (MI). In a neonatal heart MI model, we found that Apln-CreER-labelled capillary endothelial cells do not contribute to the large collateral arteries. Instead, these large collateral arteries mainly arise from pre-existing, infrequently labelled coronary arteries, indicative of arteriogenesis. Furthermore, in an adult heart MI model, Apln-CreER activity also distinguishes large and small diameter arteries from capillaries. Lineage tracing in this setting demonstrated that most large and small coronary arteries in the infarcted myocardium and border region are derived not from capillaries, but from pre-existing arteries. Apln-CreER-mediated lineage tracing distinguishes capillaries from large arteries, in both the neonatal and adult hearts. Through genetic fate mapping, we demonstrate that pre-existing arteries, but not capillaries, extensively contribute to collateral artery formation following myocardial injury. These results suggest that arteriogenesis is the major mechanism underlying collateral vessel formation.