NFkappaB is a Key Player in the Crosstalk between Inflammation and Cardiovascular Diseases

Abstract

Inflammation is a key mechanism of cardiovascular diseases. It is an essential component of atherosclerosis and a significant risk factor for the development of cardiovascular events. In the crosstalk between inflammation and cardiovascular diseases, the transcription factor NFκB seems to be a key player since it is involved in the development and progression of both inflammation and cardiac and vascular damage. In this review, we deal with the recent findings of the role of inflammation in cardiac diseases, focusing, in particular, on NFκB as a functional link. We describe strategies for the therapeutic targeting of NFκB as a potential strategy for the failing heart.

Keywords: GRK; NFκB; cardiovascular diseases; inflammation.

Figure 1

Pro-inflammatory cytokines (TNFα, IL-6, IL1β, TGF-1β) are released in response to myocardial infarction. These cytokines exert different effects on acute and chronic responses. In an early phase, they exert a cardioprotective role by regulating the survival of cardiomyocytes in the infarcted area while in chronic responses these cytokines favor cardiac remodeling.

Figure 2

The inhibition of NFκB signaling can occur at different steps of its activation pathway. Several inhibitors have been designed which act on IκBα degradation (TP-110), IKK activity (EF-24), NFκB nuclear translocation (SN-50), and DNA binding (tacrolimus).

Figure 3

Two novel inhibitors have been designed based on the structure of GRKs. Ant124, which reproduces the HJ loop of GRK2, inhibits NFkB activation by blocking IκBα degradation. TAT-RH, which reproduces the RH domain of GRK5, binds IκBα and blocks the complex IκBα/NFκB in the nucleus thus preventing NFκB activation.