Prevention of age-induced N(epsilon)-(carboxymethyl)lysine accumulation in the microvasculature

Wessel W. Fuijkschot*, Hjalmar J. de Graaff, Ekatarina Berishvili, Zurab Kakabadze, Koba Kupreishvili, Elisa Meinster, Maaike Houtman, Amber van Broekhoven, Casper G. Schalkwijk, Alexander B. A. Vonk, Paul A. J. Krijnen, Yvo M. Smulders, Hans W. N. Niessen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


ObjectiveN(epsilon)-(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. Materials and methodsApoE(-/-) 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. ResultsCardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 1185 [592-1460] at 40 weeks, to 3317 [1760-4715] at 70 weeks (P = 0005). At the same time points, cerebral microvascular CML increased from 645; [478-730] to 1299; [985-20122] (P = 0003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [3317; (1760-4715) vs. 1473; (444-2816) P = 0037]. No such effects were found in the brain. ConclusionsAccumulation of N(epsilon)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice.
Original languageEnglish
Pages (from-to)334-341
JournalEuropean Journal of Clinical Investigation
Issue number4
Publication statusPublished - Apr 2016


  • Advanced glycation end products
  • age-related pathology
  • docosahexaenoic acid
  • microvasculature
  • N(epsilon)-(carboxymethyl)lysine (CML)


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