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

IF 1.1 4区医学 Q4 TOXICOLOGY

Molecular & Cellular Toxicology Pub Date : 2024-02-01 DOI:10.1007/s13273-023-00420-8

{"title":"CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating MAPK/p38 pathway in combination with NOD2","authors":"","doi":"10.1007/s13273-023-00420-8","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Objective</h3> <p>This study aimed to uncover the related mechanism of CARD9 in myocardial inflammation, oxidative stress, and vascular dysfunction following hypertension.</p> </span> <span> <h3>Methods</h3> <p>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.</p> </span> <span> <h3>Results</h3> <p>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.</p> </span> <span> <h3>Conclusion</h3> <p>CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating the MAPK/p38 pathway in combination with NOD2.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"183 1","pages":""},"PeriodicalIF":1.1000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular & Cellular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13273-023-00420-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

CARD9 与 NOD2 共同激活 MAPK/p38 通路，调节高血压大鼠的心肌炎症、氧化应激和血管功能障碍

摘要目的本研究旨在揭示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。方法给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。收获心脏组织和主动脉组织，用 HE 染色法观察病理损伤，用 TUNEL 染色法观察细胞凋亡，用 IHC 染色法观察α-SMA、胶原 I 和胶原 II 的表达。此外，还测定了心脏组织的炎症反应和氧化应激。采用 CO-IP 法检测 CARD9 与 NOD2 的结合。通过 Western 印迹检测基因蛋白表达。结果 CARD9 和 NOD2 在高血压大鼠心肌中过度表达。敲除 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，而过表达 NOD2 则效果相反。CARD9与NOD2结合。NOD2 的过表达可以挽救 CARD9 敲除所产生的保护作用。CARD9 通过靶向 NOD2 激活了 MAPK/p38 通路。结论 CARD9 通过与 NOD2 结合激活 MAPK/p38 通路，调节高血压大鼠的心肌炎症、氧化应激和血管功能障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular & Cellular Toxicology 医学-毒理学

CiteScore

2.50

自引率

17.60%

发文量

114

审稿时长

6-12 weeks

期刊介绍： Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.