title: Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet.
abstract: BACKGROUND
  Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin-sensitive controls but the mechanisms that mediate this atherosclerosis phenotype are unknown.
  
  
  OBJECTIVE
  To determine the metabolic parameters that associate with the severity of coronary atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet.
  
  
  METHODS
  The primary endpoint was severity of coronary atherosclerosis in adult pigs (Sus scrofa, n = 37) fed a high fat diet that also contained high NaCl (56% above recommended levels) for 1 year.
  
  
  RESULTS
  Twenty pigs developed severe and diffuse distal coronary artery atherosclerosis (i.e., severe = intimal area as a percent medial area > 200% in at least 2 coronary artery cross sections and diffuse distal = intimal area as a percent medial area ≥ 150% over 3 sections separated by 2 cm in the distal half of the coronary artery). The other 17 pigs had substantially less coronary artery atherosclerosis. All 37 pigs had blood pressure in a range that would be considered hypertensive in humans and developed elevations in total and LDL and HDL cholesterol, weight gain, increased backfat, and increased insulin resistance (Bergman Si) without overt diabetes. Insulin resistance was not associated with atherosclerosis severity. Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis. Most importantly, the 20 high fat/high NaCl diet-fed pigs with severe and diffuse distal coronary artery atherosclerosis had substantially greater increases (p< 0.05) in oxidized LDL (oxLDL) and fructosamine consistent with increased protein glycation.
  
  
  CONCLUSIONS
  In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Nichols
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Merricks
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Dwight A
authors.initials: DA
authors.lastname: Bellinger
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Raymer
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Lam
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Koch
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Walker H
authors.initials: WH
authors.lastname: Busby
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Clemmons
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology; D004195:Disease Models, Animal; D019270:Fructosamine / Q000097:blood*; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000097:blood*; D012720:Severity of Illness Index; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*; D034421:Sus scrofa
chemical_list: D008077:Lipoproteins, LDL; D017673:Sodium Chloride, Dietary; C099252:oxidized low density lipoprotein; D019270:Fructosamine