Human recombinant leptin-induced nitric oxide release from endothelium depends on the membrane localization pattern of endothelial nitric oxide synthase.

The form of nitric oxide (NO) released from endothelial nitric oxide synthase (eNOS) can influence various aspects of the angiogenic process. The endogenous hormone leptin can induce different physiological processes, such as angiogenesis, at low concentrations. Several studies suggest that leptin's ability to induce endothelium-dependent vascular relaxation is mediated by stimulating NO through distinct signalling pathways. Therefore, an attempt has been made to understand the optimal concentration and incubation time of human recombinant leptin for the enzymatic release of NO from eNOS. Changes in the localisation and phosphorylation pattern of eNOS in cultured endothelium under different concentrations and incubation times are examined. Five nanomolar concentration of human recombinant leptin, within 6 min of incubation, can induce a significant level of NO from activated eNOS in cultured endothelium through plasma membrane localisation and phosphorylation of eNOS. Our findings suggest that human recombinant leptin can modulate NO-dependent pathways, opening new therapeutic avenues for angiogenesis-related disorders, such as wound healing, when used at appropriate concentrations and incubation times. This capacity of human recombinant leptin supports its potential therapeutic application in pathological conditions like ischaemic heart diseases and wound healing processes, where angiogenesis requires early intervention.