title: Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature.
abstract: OBJECTIVE
  N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and nondiabetics. CML depositions in the microvasculature have recently been linked to the aetiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesized that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and antioxidative actions.
  
  
  METHODS
  ApoE(-/-) mice (n = 50) were fed a Western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n = 20) were fed a Western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry.
  
  
  RESULTS
  Cardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 11·85 [5·92-14·60] at 40 weeks, to 33·17 [17·60-47·15] at 70 weeks (P = 0·005). At the same time points, cerebral microvascular CML increased from 6·45; [4·78-7·30] to 12·99; [9·85-20·122] (P = 0·003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [33·17; (17·60-47·15) vs. 14·73; (4·44-28·16) P = 0·037]. No such effects were found in the brain.
  
  
  CONCLUSIONS
  Accumulation of N(ε)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice.
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.|Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.|Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Wessel W
authors: WW
authors: Fuijkschot
authors: Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.|Department of Cardiac Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors: Hjalmar J
authors: HJ
authors: de Graaff
authors: Georgian National Institute of Medical Research, Ilia State University, Tbilisi, Georgia.
authors: Ekatarina
authors: E
authors: Berishvili
authors: Georgian National Institute of Medical Research, Ilia State University, Tbilisi, Georgia.
authors: Zurab
authors: Z
authors: Kakabadze
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.|Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.
authors: Koba
authors: K
authors: Kupreishvili
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Elisa
authors: E
authors: Meinster
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Maaike
authors: M
authors: Houtman
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Amber
authors: A
authors: van Broekhoven
authors: Department of Internal Medicine, Maastricht University, Maastricht, the Netherlands.
authors: Casper G
authors: CG
authors: Schalkwijk
authors: Department of Cardiac Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors: Alexander B A
authors: AB
authors: Vonk
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.|Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.
authors: Paul A J
authors: PA
authors: Krijnen
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.|Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Yvo M
authors: YM
authors: Smulders
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.|Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.|Department of Cardiac Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors: Hans W N
authors: HW
authors: Niessen
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001921:Brain / Q000098:blood supply; D003331:Coronary Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008815:Mice, Inbred Strains; D055806:Microvessels / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate; D000099156:Superoxide Dismutase 2
chemical_list: D001057:Apolipoproteins E; D008239:Lysine; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C048496:N(6)-carboxymethyllysine
keywords: Advanced glycation end products; N(ε)-(carboxymethyl)lysine (CML); age-related pathology; docosahexaenoic acid; microvasculature