title: Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice.
abstract: OBJECTIVE
  There are several pathways that mediate the aberrant metabolism of glucose and that might induce greater vascular damage in the setting of diabetes. The polyol pathway mediated by aldose reductase (AR) has been postulated to be one such pathway. However, it has been reported that AR reduces toxic lipid aldehydes and, under some circumstances, might be antiatherogenic.
  
  
  RESULTS
  Atherosclerosis development was quantified in 2 lines of transgenic mice expressing human AR (hAR) crossed on the apolipoprotein E knockout background. The transgenes were used to increase the normally low levels of this enzyme in wild-type mice. Both generalized hAR overexpression and hAR expression via the Tie 2 promoter increased lesion size in streptozotocin diabetic mice. In addition, pharmacological inhibition of AR reduced lesion size.
  
  
  CONCLUSIONS
  Although in some settings AR expression might reduce levels of toxic aldehydes, transgenic expression of this enzyme within the artery wall leads to greater atherosclerosis.
authors.affiliation: Division of Endocrinology, New York University Langone Medical Center, NY 10016, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Vedantham
authors.forename: HyeLim
authors.initials: H
authors.lastname: Noh
authors.forename: Radha
authors.initials: R
authors.lastname: Ananthakrishnan
authors.forename: Ni
authors.initials: N
authors.lastname: Son
authors.forename: Kellie
authors.initials: K
authors.lastname: Hallam
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: Shuiquing
authors.initials: S
authors.lastname: Yu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Shen
authors.forename: Rosa
authors.initials: R
authors.lastname: Rosario
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Thyyar
authors.initials: T
authors.lastname: Ravindranath
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Drosatos
authors.forename: Lesley Ann
authors.initials: LA
authors.lastname: Huggins
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D048909:Diabetes Complications / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000449:Aldehyde Reductase; D005947:Glucose