Flow-dependent remodeling of small arteries in mice deficient for tissue-type transglutaminase - Possible compensation by macrophage-derived factor XIII
Flow-dependent remodeling of small arteries in mice deficient for tissue-type transglutaminase - Possible compensation by macrophage-derived factor XIII
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DOI：
10.1161/01.res.0000229657.83816.a7
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发表时间：
2006-07-07
影响因子：
20.1
通讯作者：
VanBavel, Ed
中科院分区：
文献类型：
--
作者：
Bakker, Erik N. T. P.;Pistea, Adrian;VanBavel, Ed
血流的慢性变化导致血管口径的适应。因此，动脉在血流量减少后显示向内重塑。我们假设这种重塑依赖于交联酶组织型谷氨酰胺转氨酶(TTG)。在野生型(WT)和tTG缺失的小鼠中，利用手术施加的肠系膜小动脉血流改变来研究血流依赖性重构。WT小鼠在低血流量2天后出现向内重构，而tTG缺失的小鼠动脉中没有这种情况。然而，在持续低血流量7天后，WT和tTG缺失小鼠的动脉向内重塑相似。研究重塑的不同途径，我们发现血浆转谷氨酰胺酶XIII因子在WT和tTG缺失小鼠的动脉中表达相对较高。此外，来自wt和ttg基因缺失的小鼠的血管都显示了转谷氨酰胺酶特异性的交联链。在tTG缺失小鼠暴露于低血流的血管中，发现外膜单核/巨噬细胞聚集。由于单核/巨噬细胞可能是XIII因子的来源，tTG缺失的小鼠被脂质体包裹的氯屈膦酸盐治疗。脂质体包裹的氯屈膦酸盐消除单核/巨噬细胞可减少因子XIII的表达和tTG缺失小鼠的内向重构。综上所述，tTG在与血流减少相关的小动脉内向重构中起重要作用。在tTG缺失的小鼠中，外膜单核/巨噬细胞是XIII因子的来源之一，当tTG缺失时，外膜单核/巨噬细胞参与了另一种延迟的内向重构机制。
Chronic changes in blood flow induce an adaptation of vascular caliber. Thus, arteries show inward remodeling after a reduction in blood flow. We hypothesized that this remodeling depends on the crosslinking enzyme tissue-type transglutaminase (tTG). Flow-dependent remodeling was studied in wild-type (WT) and tTG-null mice using a surgically imposed change in blood flow in small mesenteric arteries. WT mice showed inward remodeling after 2 days of low blood flow, which was absent in arteries from tTG-null mice. Yet, after continued low blood flow for 7 days, inward remodeling was similar in arteries from WT and tTG-null mice. Studying the alternative pathways of remodeling, we identified a relatively high expression of the plasma transglutaminase factor XIII in arteries of WT and tTG-null mice. In addition, vessels from both WT and tTG-null mice showed the presence of transglutaminase-specific crosslinks. An accumulation of adventitial monocytes/macrophages was found in vessels exposed to low blood flow in tTG-null mice. Because monocytes/macrophages may represent a source of factor XIII, tTG-null mice were treated with liposome-encapsulated clodronate. Elimination of monocytes/macrophages with liposome-encapsulated clodronate reduced both the expression of factor XIII and inward remodeling in tTG-null mice. In conclusion, tTG plays an important role in the inward remodeling of small arteries associated with decreased blood flow. Adventitial monocytes/macrophages are a source of factor XIII in tTG-null mice and contribute to an alternative, delayed mechanism of inward remodeling when tTG is absent.