Fig. 4: Vascular regulation and copper in CVD. | Cell Death & Disease

Fig. 4: Vascular regulation and copper in CVD.

From: Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

Fig. 4

Copper can regulate the activity of HIF-1. HIF-1 consists of HIF-1α and HIF-1β. CCS transports copper into the nucleus, and CuBP mediates subsequent actions of copper. The core base “GGAA” (the core motif of the ETS family) is a key motif in the binding site of copper-dependent genes. p300, CBP, and SRC1 act as cofactors to form the HIF-1 transcription complex. The interaction of HIF-1 with HRE requires copper to initiate the copper-dependent expression of genes such as VEGF. LOX is essential for vascular maturation. Copper can regulate LOX production through ATOX1, ATP7A, and RAC1. Ischemia and hypoxia increase the efflux of copper. The inhibition of the above mechanisms caused by copper efflux will bring about vascular wall hypotonia, increased myocardial fragility, and angiogenesis depression, and will eventually lead to myocardial damage. ATOX1 antioxidant 1 copper chaperone, ATP7A ATPase copper transporting alpha, BNIP3 BCL2 interacting protein 3, CCS Cu chaperone for SOD1, CTR1 calcitonin receptor 1, ETS E-twenty-six, HIF hypoxia inducible factor, HRE hypoxia-responsive element, LOX lysyl oxidase, RAC1 ras-related C3 botulinum toxin substrate 1, TGN trans Golgi network, VEGF vascular endothelial growth factor. The figure was created with Figdraw (https://www.figdraw.com/).

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