title: Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage.
abstract: The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage.
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. cecilia.nigro@alice.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. cecilia.nigro@alice.it.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nigro
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. aleleone86@libero.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. aleleone86@libero.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Leone
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. gregoryraciti@gmail.com.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. gregoryraciti@gmail.com.
authors.forename: Gregory Alexander
authors.initials: GA
authors.lastname: Raciti
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. mi_longo@libero.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. mi_longo@libero.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Longo
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. paolamirra.lib@libero.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. paolamirra.lib@libero.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Mirra
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. fpietro@unina.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. fpietro@unina.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. beguino@unina.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. beguino@unina.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. c.miele@ieos.cnr.it.|Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. c.miele@ieos.cnr.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Miele
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D008954:Models, Biological; D011765:Pyruvaldehyde / Q000378:metabolism; D014652:Vascular Diseases / Q000201:enzymology*
chemical_list: D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase
keywords: glyoxalase; insulin-resistance; methylglyoxal; vascular function