Department of Biology, Institut National de la Santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France; Fédération Hospitalo-Universitaire REMODeling in Valvulopathy and Heart Failure, Rouen, France.
Department of Biology, Institut National de la Santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France; Fédération Hospitalo-Universitaire REMODeling in Valvulopathy and Heart Failure, Rouen, France; Department of Cardiology, Rouen University Hospital, 76031 Rouen Cedex, France.
J Integr Med. 2019 Mar;17(2):107-114. doi: 10.1016/j.joim.2019.01.010. Epub 2019 Jan 30.
The use of animal models of aortic stenosis (AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed; data have indicated that while aortic regurgitation (AR) is effectively induced, development of AS is rare. We aimed to evaluate the effect of high-fat diet (HFD) and vitamin D supplementation in this model.
HFD and subcutaneous vitamin D injections were initiated at the age of 6 weeks until the age of 6 (n = 16, 6-month treatment group) and 9 (n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis (calcium, 1,25(OH)D and cholesterol), histology and immunohistochemistry (CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment (6 or 9 months).
Total cholesterol and 1,25(OH)D were significantly increased relative to the control group. HFD and vitamin D supplementation did result in improvements to the model, since AS was only detected in 6 (15.3%) mice (2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.
These results suggest that HFD and vitamin D supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.
使用主动脉瓣狭窄（AS）动物模型对于进一步阐明其病理生理学和评估新的治疗策略仍然至关重要。已经提出了波动-2 小鼠 AS 模型；数据表明，虽然有效地诱导了主动脉瓣反流（AR），但 AS 的发展却很少见。我们旨在评估高脂肪饮食（HFD）和维生素 D 补充在此模型中的作用。
在 6 周龄至 6 （n=16，6 个月治疗组）和 9 （n=11，9 个月治疗组）个月龄时开始给予 HFD 和皮下维生素 D 注射。12 只未补充的波动-2 小鼠作为对照组。在 3、6 和 9 个月时进行超声心动图检查。在实验结束时（6 或 9 个月）评估血清分析（钙，1,25（OH）D 和胆固醇），组织学和免疫组织化学（CD-31，CD-68 和骨桥蛋白）。
与对照组相比，总胆固醇和 1,25（OH）D 明显增加。HFD 和维生素 D 补充确实改善了该模型，因为只有 6 只（3 组中的 2 只）小鼠检测到 AS，而其余动物则发生了 AR。超声心动图参数、纤维化、厚度、炎症和瓣膜钙化在 6 个月治疗组和对照组之间没有显著差异。在 9 个月治疗组中也观察到了类似的结果。
这些结果表明，HFD 和维生素 D 补充对波动-2 小鼠模型没有影响。该模型主要模拟 AR，很少模拟 AS。需要进一步的研究来找到一种可靠的 AS 动物模型。
