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

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

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.

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.

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