Development of Abdominal Aortic Aneurysm Is Decreased in Mice with Plasma Phospholipid Transfer Protein Deficiency
Development of Abdominal Aortic Aneurysm Is Decreased in Mice with Plasma Phospholipid Transfer Protein Deficiency
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DOI：
10.1016/j.ajpath.2013.05.018
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发表时间：
2013-09-01
影响因子：
6
通讯作者：
Lagrost, Laurent
中科院分区：
文献类型：
--
作者：
Deckert, Valerie;Kretz, Benjamin;Lagrost, Laurent
血浆磷脂转移蛋白（PLTP）增加促动脉粥样硬化脂蛋白的循环水平，加速血液凝固，并调节炎症。通过在小鼠主动脉的一个部位处使用机械和弹性蛋白酶损伤的组合（弹性蛋白酶模型）或在高脂血症ApoE敲除小鼠中连续输注血管紧张素II（Ang II模型）来研究PLTP在腹主动脉瘤（AAA）发展中的作用。在弹性蛋白酶模型中，PLTP完全缺乏与AAA发生率显著降低和AAA扩张程度降低相关。对于Ang II模型，发现与弹性蛋白酶模型中的那些一致，其中在PLTP缺陷小鼠中具有较低的严重程度等级，在PLTP缺陷杂合子中具有中间表型，并且当限制于骨髓来源的免疫细胞时，PLTP缺陷性状的作用减弱。腹主动脉瘤中全身PLTP缺乏的保护作用进一步通过PLTP缺乏小鼠的外膜扩张程度较低、弹性蛋白降解减少、招募的巨噬细胞较少和平滑肌细胞消耗较少（与野生型小鼠相比）来说明，如主动脉切片的比较显微镜分析所示。最后，累积的证据支持PLTP缺乏与基质金属蛋白酶（已知降解弹性蛋白和胶原蛋白）的表达和活性水平降低相关。我们的结论是，PLTP可以发挥重要作用，在AAA的病理生理。
Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly tower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity Levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.