Intracellular hyperglycaemia activates PKC-β and -δ isoforms, which induce activation of pro-inflammatory genes [e.g. p38 and nuclear factor kappa-light-chain-enhancer of activated B cell (NK-κB)] and microvascular matrix remodelling, impair vascular permeability and inhibit endothelial nitric oxide synthase (eNOS) [34–38]. Here, NOS3 is linked to Hyperglycemia.