Targeting the ACE2 and Apelin Pathways Are Novel Therapies for Heart Failure: Opportunities and Challenges

Figure 1

The enzymatic cascade involved in the renin-angiotensin system, key receptor systems, and the biological effects mediated by Ang II and Ang 1–7. Solid black lines, enzymatic pathways; Broken lines, peptide agonist interacting with its key receptor; Green arrow, stimulatory effects; Red arrow, pathologic effects; Green bars; inhibitory effects. ACE2: angiotensin-converting enzyme; Akt: protein kinase B; Ang: angiotensin; APA: aminopeptidase A; AT1R Ang II type 1 receptor; CHOP: CCAAT/enhancer binding protein homologous protein; Cox-2: cyclooxygenase-2; CPA: carboxypeptidase A; eNOS: endothelial synthase; ERK: extracellular signal-regulated kinase; GRP-78: glucose regulated protein; IL-6: interleukin-6; JAK-STAT: Janus Kinase- signal transducer and activator of transcription system; JNK: C-jun-N-terminal kinase; MAPK: mitogen activated protein kinase; Mas R: Ang 1–7 receptor; MCP-1: monocyte cheomattractant protein 1; MMIF: macrophage migration inhibitory factor; MMP: matrix metalloproteinase; NADPH: nicotinamide adenine dinucleotide phosphate; NEP: neutral endopeptidase; NF-kappaB: nuclear factor kappa-light-chain-enhancer of activated B cells; NO: nitric oxide; PCP: prolyl carboxypeptidase (also known as angiotensinase C); PEP: prolyl endopeptidase; PI3K: phosphatidylinositol 3-kinases; PKC: protein kinase C; ROS: reactive oxygen species; SOD: superoxide dismutase; TGFβ1, transforming growth factorβ1; TNF α: tumor necrosis factor α; VCAM-1: vascular cell adhesion molecule-1.