Potential Role of Nuclear FactorκB in Diabetic Cardiomyopathy

Abstract

Diabetic cardiomyopathy entails the cardiac injury induced by diabetes independently of any vascular disease or hypertension. Some transcription factors have been proposed to control the gene program involved in the setting and development of related processes. Nuclear factor-kappa B is a pleiotropic transcription factor associated to the regulation of many heart diseases. However, the nuclear factor-kappa B role in diabetic cardiomyopathy is under investigation. In this paper, we review the nuclear factor-kappa B pathway and its role in several processes that have been linked to diabetic cardiomyopathy, such as oxidative stress, inflammation, endothelial dysfunction, fibrosis, hypertrophy and apoptosis.

Regulation of Large Conductance Ca2+-activated K+ (BK) Channel β1 Subunit Expression by Muscle RING Finger Protein 1 in Diabetic Vessels

“…It is known that NF-B activation is a key event for the initiation of cardiovascular pathogenesis in diabetes as a result of increased oxidative stress (56,57). We found that the protein levels of the NF-B1/p50 and p65 subunits were augmented in diabetic vessels and in HG-cultured human coronary SMCs.…”

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

“…Much of the inflammatory response in diabetic cardiomyocytes is attributed to activation of the transcription factor NF‐κB by elevations in ROS,113 although increased levels of cytokines, chemokines, adhesion molecules and infiltrating leucocytes are also important in this process. In experimental STZ‐induced T1D models of diabetic cardiomyopathy, NF‐κB activation was shown to be correlated with the increased release of IL‐1β and TNF‐α 113, 114, 115. Moreover, elevated levels of these two pro‐inflammatory cytokines have been found in the circulation and hearts of patients with T2D 116.…”

“…Moreover, elevated levels of these two pro‐inflammatory cytokines have been found in the circulation and hearts of patients with T2D 116. In fact, several studies report a strong correlation between the characteristic hallmarks of diabetic cardiomyopathy and the levels NF‐κB and cytokines 113. It should be noted that cardiomyocytes and fibroblasts express receptors for IL‐1β and TNF‐α.…”

“…Upon binding of IL‐1β and TNF‐α to their respective receptors, a signal transduction pathway is activated which stimulates NF‐κB, resulting in a positive feedback loop that contributes to the intensification of diabetes‐induced inflammation in the myocardium. Once activated, NF‐κB, additionally drives the expression of numerous growth factors, such as connective tissue growth factor (CTGF) and TGF‐β 113. This, in turn, drives the production of extracellular matrix (ECM) proteins in the heart, including collagen, fibronectin and proteoglycans, leading to fibrosis, LV remodelling and stiffness, and reduced relaxation of the heart 108, 117.…”

Influence of naringin on the myocardial ultrastructure and NF-B expression in rats with diabetic cardiomyopathy

“…Clinical and experimental studies have shown that inflammatory reactions possibly play an important role in the development of diabetic cardiomyopathy (DC) (Dasu et al, 2008;Jiao et al, 2009;Van Linthout et al, 2007;Westermann et al, 2009;Lorenzo O et al, 2011). Nuclear factor-kappa B (NF-κB) is the key factor in the inflammation signal pathway.…”