University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
Atherosclerosis. 2021 Feb;318:8-13. doi: 10.1016/j.atherosclerosis.2020.11.032. Epub 2020 Dec 1.
Genetic variations between C57Bl/6 mouse substrains are highly relevant to the investigation of cardiovascular disease. We here assessed whether these variations have an impact on the incidence of abdominal aortic aneurysms (AAA) in C57Bl/6J and 6 N mice.
AAA were induced by subcutaneous infusion of 1500 ng/kg*min Angiotensin-II for four weeks in six-month-old male CB57Bl/6J and 6N mice. Aortic smooth muscle cells (VSMC) were isolated from untreated animals for in vitro analysis.
C57Bl/6J mice are more susceptible to AAA formation (76.5% vs. 7.1%, p = 0.0002). C57Bl/6J VSMC expressed more pro-inflammatory molecules such as Nlrp3, Aim2 and NF-κB. Additionally, these cells presented significantly higher levels of NADP/NADPH and oxidative DNA modifications, as indicated by 8-OHdG-staining, compared to C57Bl/6N VSMC.
In contrast to previous reports, we present evidence that six-month-old C57BL/6J, but not C57BL/6N mice develop AAA. In accordance with the deficiency of nicotinamide-nucleotide-transhydrogenase (Nnt), C57BL/6J VSMC displayed increased oxidative stress, oxidative DNA damage and a stronger inflammatory phenotype than C57BL/6N VSMC.
C57Bl/6 小鼠亚系之间的遗传变异与心血管疾病的研究密切相关。本研究旨在评估这些变异是否会影响 C57Bl/6J 和 6N 小鼠腹主动脉瘤（AAA）的发生率。
在 6 个月大的雄性 CB57Bl/6J 和 6N 小鼠中，通过皮下输注 1500ng/kg*min 血管紧张素-II 四周来诱导 AAA。从未处理的动物中分离出主动脉平滑肌细胞（VSMC）用于体外分析。
C57Bl/6J 小鼠更容易形成 AAA（76.5% vs. 7.1%，p=0.0002）。C57Bl/6J 的 VSMC 表达了更多的促炎分子，如 Nlrp3、Aim2 和 NF-κB。此外，与 C57Bl/6N VSMC 相比，这些细胞的 NADP/NADPH 和氧化 DNA 修饰水平明显更高，如 8-OHdG 染色所示。
与之前的报道相反，本研究提供了证据表明，六个月大的 C57BL/6J 而不是 C57BL/6N 小鼠会发展为 AAA。与烟酰胺核苷酸转氢酶（Nnt）的缺乏一致，C57BL/6J 的 VSMC 表现出更强的氧化应激、氧化 DNA 损伤和炎症表型，比 C57BL/6N VSMC 更为明显。
