Peiró Vallejo, ConcepciónMatesanz, NuriaNevado, JuliánLafuente, NuriaCercas, ElenaAzcutia Criado, VerónicaVallejo, SusanaRodríguez-Mañas, LeocadioSánchez-Ferrer, Carlos F.2024-02-092024-02-092003-10-01Peiró, Concepción, et al. «Glycosylated Human Oxyhaemoglobin Activates Nuclear Factor‐ κ B and Activator Protein‐1 in Cultured Human Aortic Smooth Muscle». British Journal of Pharmacology, vol. 140, n.o 4, octubre de 2003, pp. 681-90. DOI.org (Crossref), https://doi.org/10.1038/sj.bjp.0705483.0007-118810.1038/sj.bjp.0705483https://hdl.handle.net/20.500.14352/1007461 Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-kB (NF-kB), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes. 2 In this study, we analysed whether Amadori-modified human oxyhaemoglobin, glycosylated at either normal (N-Hb) or elevated (E-Hb) levels, can induce cell growth and activate AP-1 and NF-kB in cultured human aortic smooth muscle cells (HASMC). 3 E-Hb (1 nM–1 mM), but not N-Hb, promoted a concentration-dependent increase in cell size from nanomolar concentrations, although it failed to stimulate HASMC proliferation. At 10 nM, E-Hb stimulated both AP-1 and NF-kB activity, as assessed by transient transfection, electromobility shift assays or immunofluorescence staining. The effects of E-Hb resembled those of the proinflammatory cytokine tumour necrosis factor-a (TNF-a). E-Hb enhanced intracellular superoxide anions content and its effects on HASMC were abolished by different ROS scavengers. 4 In conclusion, E-Hb stimulates growth and activates AP-1 and NF-kB in human vascular smooth muscle by redox-sensitive pathways, thus suggesting a possible direct role for Amadori adducts in diabetic vasculopathy.engjournal article1476-5381https://doi.org/10.1038/sj.bjp.0705483https://pubmed.ncbi.nlm.nih.gov/14504138/restricted access615.01/.03Diabetic vasculopathyAmadori adductsReactive oxygen speciesHuman vascular smooth muscleMedicina32 Ciencias Médicas3209 Farmacología