Abstract

Objective

This study aimed to uncover the related mechanism of CARD9 in myocardial inflammation, oxidative stress, and vascular dysfunction following hypertension.

Methods

Spontaneous hypertension rats were injected with shRNA adenovirus vector or adenovirus overexpression vector. Blood pressure was measured. Cardiac tissue and aortic tissue were harvested to observe pathological damage by HE staining and apoptosis by TUNEL staining, as well as expression of α-SMA, Collagen I, and Collagen II by IHC staining. In addition, inflammatory response and oxidative stress in cardiac tissues were determined. CO-IP assay was employed to examine the binding of CARD9 to NOD2. Gene protein expression was measured by Western blot.

Results

CARD9 and NOD2 were overexpressed in the myocardium of hypertensive rats. Knocking down CARD9 improved myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats, whereas overexpressing NOD2 had the opposite result. CARD9 was bound to NOD2. NOD2 overexpression rescued the protective impacts of CARD9 knockdown. CARD9 activated the MAPK/p38 pathway by targeting NOD2.

Conclusion

CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating the MAPK/p38 pathway in combination with NOD2.

中文翻译：

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CARD9联合NOD2激活MAPK/p38通路调节高血压大鼠心肌炎症、氧化应激和血管功能障碍

摘要

客观的

本研究旨在揭示CARD9在高血压后心肌炎症、氧化应激和血管功能障碍中的相关机制。

方法

自发性高血压大鼠注射shRNA腺病毒载体或腺病毒过表达载体。测量血压。采集心脏组织和主动脉组织，HE染色观察病理损伤，TUNEL染色观察细胞凋亡，IHC染色观察α-SMA、I型胶原和II型胶原的表达。此外，还测定了心脏组织的炎症反应和氧化应激。 CO-IP 测定用于检查 CARD9 与 NOD2 的结合。通过蛋白质印迹测量基因蛋白表达。

结果

CARD9和NOD2在高血压大鼠的心肌中过度表达。敲低 CARD9 可改善高血压大鼠的心肌炎症、氧化应激和血管功能障碍，而过度表达 NOD2 则会产生相反的结果。 CARD9 与 NOD2 结合。 NOD2 过表达挽救了 CARD9 敲低的保护作用。 CARD9 通过靶向 NOD2 激活 MAPK/p38 通路。

结论

CARD9 通过与 NOD2 结合激活 MAPK/p38 通路来调节高血压大鼠的心肌炎症、氧化应激和血管功能障碍。