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

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.