Fig. 3.

Diagram of the proposed signalling pathway involved in the cardiac remodelling process in the absence of natriuretic peptide receptor-A (NPRA)/cGMP signalling. Disruption of atrial natriuretic peptide (ANP)/NPRA signalling leads to increased activation of the renin–angiotensin system (RAS). Activation of the RAS has been shown to activate increased generation of reactive oxygen species (ROS). This leads to activation and dissociation of nuclear factor (NF)-kB and activator protein (AP)-1 transcription factor subunits from the complex in the cytoplasm and translocation into the nucleus, which activates pro-inflammatory cytokine genes, leading to medial thickening and perivascular fibrosis, in turn promoting cardiac remodelling, hypertrophy and heart failure. KHD, kinase homology domain; GC, guanylate cyclase; AngII, angiotensin II. Reproduced with permission from Vellaichamy et al.¹⁶