CD40L/CD40 Regulates Adipokines and Cytokines by H3K4me3 Modification in Epicardial Adipocytes

Abstract: Epicardial adipose tissue (EAT) dysfunction mediates chronic inflammation by regulating inflammation-related adipokines and cytokines, and it further promotes coronary artery disease (CAD) development. CD40L/CD40 is involved in multiple inflammatory pathways that contribute to various pathophysiological processes. However, the function of CD40L/CD40 in the expression and production of adipokines and cytokines in epicardial adipocytes remains unclear. The purpose of the present study was to explore the role and underlying mechanisms of CD40L/CD40 in adipokine and cytokine expression and production. We isolated adipocytes from EAT tissues of CAD and non-CAD patients. We noticed that CD40 was dramatically increased in EAT tissues of CAD patients. Loss-of-function and gain-of-function studies were performed. The results showed that CD40 silencing reduced recombinant CD40 ligand (rCD40L)–induced upregulation of plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 messenger RNA levels and secretion. Overexpression of CD40 displayed the opposite results. In addition, rCD40L triggered mixed lineage leukemia protein-1 (MLL1) expression both in messenger RNA and protein levels. CD40 depletion apparently blocked MLL1 expression, whereas gain of function of CD40 resulted in augmentation of MLL1 levels. Interestingly, chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis revealed that CD40 eliminatio...
Source: Journal of Cardiovascular Pharmacology - Category: Cardiology Tags: Original Article Source Type: research