Nachtigal Maurice, Ghaffar Abdul, Mayer Eugene P
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Am J Pathol. 2008 Jan;172(1):247-55. doi: 10.2353/ajpath.2008.070348. Epub 2007 Dec 21.
This study has examined the role of galectin-3 (GaL3), a multicompartmented N-acetyllactosamine-binding chimeric lectin, on atherogenesis in the ApoE-deficient mouse model of atherosclerosis. Pathological changes consisting of atheromatous plaques, atherosclerotic microaneurysms extending into periaortic vascular channels, and adventitial and periaortic inflammatory infiltrates were assessed in an equal number (n = 36) of apolipoprotein (Apo)E-deficient mice and ApoE-GaL3 double-knockout mice. These mice were divided into three age groups, 21 to 23 weeks, 25 to 31 weeks, and 36 to 44 weeks of age. Results of this morphological analysis have shown an age-related increase in the incidence of aorta atheromatous plaques and periaortic vascular channels in ApoE-deficient mice. By contrast ApoE/GaL3 double-knockout mice did not show an increase in pathological changes with age. The 36- to 44-week group of ApoE(-/-)/GaL3(-/-) mice had a significantly lower number of atherosclerotic lesions (P < 0.004) and fewer atheromatous plaques (P < 0.008) when compared with ApoE(-/-)/GaL3+/+ mice of the same age. ApoE(-/-)/GaL3(-/-) mice had a lower number of perivascular inflammatory infiltrates and mast cells than those found in ApoE(-/-)/GaL3+/+ mice. The reduced number of perivascular mast cells may have resulted in a low level of interleukin-4 that contributed to the reduction in the morphological parameters of atherogenesis correlated with the lack of GaL3 expression. The effect of GaL3 deficiency on atherogenesis decrease could be related to its function as a multifunctional protein implicated in macrophage chemotaxis, angiogenesis, lipid loading, and inflammation.
本研究探讨了半乳糖凝集素-3（GaL3），一种多结构域的N-乙酰乳糖胺结合嵌合凝集素，在载脂蛋白E缺陷型动脉粥样硬化小鼠模型的动脉粥样硬化形成中的作用。在数量相等（n = 36）的载脂蛋白（Apo）E缺陷型小鼠和ApoE-GaL3双敲除小鼠中评估了由动脉粥样斑块、延伸至主动脉周围血管通道的动脉粥样硬化微动脉瘤以及外膜和主动脉周围炎性浸润组成的病理变化。这些小鼠被分为三个年龄组，分别为21至23周、25至31周和36至44周龄。这项形态学分析的结果显示，载脂蛋白E缺陷型小鼠的主动脉粥样斑块和主动脉周围血管通道的发生率随年龄增长而增加。相比之下，ApoE/GaL3双敲除小鼠并未显示出随年龄增长病理变化增加。与同年龄的ApoE（-/-）/GaL3（+/+）小鼠相比，36至44周龄的ApoE（-/-）/GaL3（-/-）小鼠的动脉粥样硬化病变数量显著减少（P < 0.004），动脉粥样斑块也更少（P < 0.008）。与ApoE（-/-）/GaL3（+/+）小鼠相比，ApoE（-/-）/GaL3（-/-）小鼠的血管周围炎性浸润和肥大细胞数量更少。血管周围肥大细胞数量减少可能导致白细胞介素-4水平降低，这有助于降低与缺乏GaL3表达相关的动脉粥样硬化形成的形态学参数。GaL3缺乏对动脉粥样硬化形成减少的影响可能与其作为一种涉及巨噬细胞趋化、血管生成、脂质负荷和炎症的多功能蛋白的功能有关。
