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

• Published in: European journal of clinical investigation Vol. 46; no. 4; pp. 334 - 341
• Main Authors: Fuijkschot, Wessel W., de Graaff, Hjalmar J., Berishvili, Ekatarina, Kakabadze, Zurab, Kupreishvili, Koba, Meinster, Elisa, Houtman, Maaike, van Broekhoven, Amber, Schalkwijk, Casper G., Vonk, Alexander B. A., Krijnen, Paul A. J., Smulders, Yvo M., Niessen, Hans W. N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2016
• Subjects: Advanced glycation end products; age-related pathology; Aging - metabolism; Animals; Apolipoproteins E - deficiency; Brain - blood supply; Coronary Vessels - metabolism; docosahexaenoic acid; Endothelium, Vascular - metabolism; Lysine - analogs & derivatives; Lysine - metabolism; Mice, Inbred Strains; microvasculature; Microvessels - metabolism; N(ε)-(carboxymethyl)lysine (CML); Superoxide Dismutase - metabolism; Survival Rate; Advanced glycation end products; N(ε)-(carboxymethyl)lysine (CML); age-related pathology; docosahexaenoic acid; microvasculature
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12599

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. Materials and 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.