Purpose: Low molecular weight carbonyl compounds, such as the -ketoaldehydes methylglyoxal (MGO) and glyoxal (GO), are formed under hyperglycemic conditions and behave as advanced glycation end product (AGE) precursors. They form adducts on proteins, thereby inducing cellular dysfunctions involved in chronic complications of diabetes. Methods and main findings: Nontoxic concentrations of GO or MGO altered the PDGF-induced PDGFR-phosphorylation, ERK1/2-activation, and nuclear translocation, and the subsequent proliferation of mesenchymal cells (smooth muscle cells and skin fibroblasts). This resulted mainly from inhibition of the intrinsic tyrosine kinase of PDGFR and in part from altered PDGF-BB binding to PDGFR. Concomitantly, the formation of AGE adducts (Ncarboxymethyl-lysine and Ncarboxyethyl-lysine) was observed on immunoprecipitated PDGFR. Arginine and aminoguanidine, used as carbonyl scavengers, reversed the inhibitory effect and the formation of AGE adducts on PDGFR. AGE-PDGFR adducts were also detected by anti-AGE antibodies in PDGFR immunopurified from aortas of diabetic (streptozotocin-treated) compared to nondiabetic apolipoprotein E-null mice. Mass spectrometry analysis of aortas demonstrated increased AGE formation in diabetic specimens. Conclusions: these data indicate that MGO and GO induce desensitization of PDGFR that helps to reduce mesenchymal cell proliferation.--Cantero, A.-V., Portero-Otín, M., Ayala, V., Auge, N., Sanson, M., Elbaz, M., Thiers, J-C., Pamplona, R., Salvayre, R., Nègre-Salvayre, A. Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-: implications for diabetic atherosclerosis.