Vascular proliferation is one of the major causes for morbidity and mortality in diabetes.However,the cellular andmolecular mechanisms that link hyperglycemia to this complication remain unclear.In present study,wedemonstrated by site-directed mutagenesis that mutated CD59 was more susceptible to glycation-inactivation forhyperglycemia.Mutated and wild-type CD59s were stably expressed in Chinese hamster ovary cells using thepALTER-MAX mammalian expression vector.Western blot,FACS and immunological fluorescence wereconducted to confirm that CD59s were tethered to the plasma membrane.Compared to wild-type CD59,humanCD59 mutants led to a significant increase in dye release assay.These results indicate that there may be somemutations of CD59 in diabetes population and the mutated CD59,which is more likely to be of glycation than thewild-type,may help to explain the distinct propensity of diabetes subjects to develop vascular proliferationcomplications.Cellular & Molecular Immunology.2005;2(4):313-317. Vascular proliferation is one of the major causes of morbidity and mortality in diabetes. Host, the cellular and molecular mechanisms that link hyperglycemia to this complication remain unclear. Present study, wedemonstrated by site-directed mutagenesis that mutated CD59 was more susceptible to glycation-inactivation forhyperglycemia. Mutated and wild-type CD59s were stably expressed in Chinese hamster ovary cells using the pALTER-MAX mammalian expression vector. Western blot, FACS and immunological fluorescence wereconducted to confirm that CD59s were tethered to the plasma membrane. Compared to wild-type CD59, humanCD59 mutants led to a significant increase in dye release assay. These results indicate that there may be somemutations of CD59 in diabetes population and the mutated CD59, which is more likely to be glycation than thewild-type, may help to explain the distinct propensity of diabetes subjects to develop vascular proliferationcomplications. Cellular & Molecular Immunology. 2005; 2 (4): 313-317.