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

Autor: Fuijkschot WW; 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., de Graaff HJ; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands.; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, the Netherlands., Berishvili E; Georgian National Institute of Medical Research, Ilia State University, Tbilisi, Georgia., Kakabadze Z; Georgian National Institute of Medical Research, Ilia State University, Tbilisi, Georgia., Kupreishvili K; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands., Meinster E; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands., Houtman M; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands., van Broekhoven A; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands., Schalkwijk CG; Department of Internal Medicine, Maastricht University, Maastricht, the Netherlands., Vonk AB; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, the Netherlands., Krijnen PA; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, the Netherlands., Smulders YM; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.; Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands., Niessen HW; 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.
Jazyk: angličtina
Zdroj: European journal of clinical investigation [Eur J Clin Invest] 2016 Apr; Vol. 46 (4), pp. 334-41. Date of Electronic Publication: 2016 Mar 03.
DOI: 10.1111/eci.12599
Abstrakt: 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.
(© 2016 Stichting European Society for Clinical Investigation Journal Foundation.)
Databáze: MEDLINE
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