BioProject

Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked-to tumorigenesis, rheumatoid arthritis and heart disease. More...

Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked-to tumorigenesis, rheumatoid arthritis and heart disease. Here we show pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RIα subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RIα knock-in mice fully resistant to PKA disulphide-activation have deficient angiogenesis in models of hind limb ischaemia and tumour-implant growth. Disulphide-activation of PKA represents a new therapeutic target in diseases with aberrant angiogenesis. The aim of this study was to identify unique differences in gene expression that may account for decreased angiogenesis in C17S PKARI knock-in mice compared with their littermate wild-types observed in cell and whole animal studies Overall design: Freshly isolated mouse aortic vessels from 3 C17S PKARI knock-in or 3 littermate wild-types were used in this study. Each vessel was divided in two rings and either left untreated or treated with VEGF. Less...