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.
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Availability of data and materials
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Ningxia Internet + telemedicine model of hypertension medical joint construction (NO.2019BEG03015).
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XX designed the research study. XBX and Fang Chen performed the research. JZ and YD provided help and advice. XJ and XT analyzed the data. XX and FM wrote the manuscript. XX and FC reviewed and edited the manuscript. All the authors contributed to editorial changes in the manuscript. All the authors read and approved the final manuscript.
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The animal experiment research protocol was approved by the Ethics Committee of Zhangye People’s Hospital Affiliated to Hexi University and performed in accordance with the “Guidelines for the care and use of experimental animals.”
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Xin, X., Zhang, J., Du, Y. et al. CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating MAPK/p38 pathway in combination with NOD2. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-023-00420-8
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DOI: https://doi.org/10.1007/s13273-023-00420-8