De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.
De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.
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DOI：
10.1016/j.yjmcc.2015.07.020
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发表时间：
2015-10
影响因子：
5
通讯作者：
Faber JE
中科院分区：
文献类型：
--
作者：
Zhang H;Faber JE
不同品系小鼠组织中原有的天然络脉的范围（数量和直径）存在很大差异，最近出现了针对人类的支持性间接证据。这种变化是闭塞性血管疾病中组织损伤严重程度的广泛变化的主要决定因素。这种遗传依赖性变异是否也存在于心脏中尚不清楚，因为不存在用于研究小鼠冠状动脉侧枝的模型。此外，由于方法学的限制，目前尚不清楚缺血是否会诱导新的冠状动脉侧枝形成（“新侧枝”），而不是先前存在的冠状侧枝的重塑。本研究试图开发一种模型来研究小鼠的冠状动脉，确定是否发生新侧支形成，并研究其机制。研究了脑和骨骼肌侧支范围已知的排序差异的四种菌株：C57BLKS>C57BL/6>A/J>BALB/c。出乎意料的是，这些菌株和另外 5 种菌株缺乏天然冠状动脉侧枝。然而，结扎后，新侧支在 1 至 2 天内迅速形成，并在 ≤ 7 天内达到最大程度。新抵押品形成的顺序与上述不同：C57BL/6>BALB/c>C57BLKS>A/J。侧支网络电导、梗塞体积−1 和收缩功能遵循相同的排序顺序。 MCP1−/− 和 CCR2−/− 小鼠的新侧支形成和侧支电导减少，梗塞体积增加。骨髓移植挽救了 CCR2−/− 小鼠侧支循环的形成。还确定了 fractalkine→CX3CR1 信号传导和内皮细胞增殖的参与。本研究引入了一种研究小鼠冠状动脉侧支循环的模型，证明冠状动脉闭塞后新侧支循环迅速形成，并发现该过程需要 MCP→CCR2 介导的骨髓细胞募集。
Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form (“neo-collaterals”) versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤ 7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume−1, and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1−/− and CCR2−/− mice. Bone-marrow transplant rescued collateral formation in CCR2−/− mice. Involvement of fractalkine→CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neocollaterals form rapidly after coronary occlusion, and finds that MCP→CCR2-mediated recruitment of myeloid cells is required for this process.