Prevention of age-induced N(ε)-(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

Research output: Contribution to journalArticleAcademicpeer-review

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.

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.

Original languageEnglish
Pages (from-to)334-341
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume46
Issue number4
DOIs
Publication statusPublished - Apr 2016

Cite this

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. / Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature. In: European Journal of Clinical Investigation. 2016 ; Vol. 46, No. 4. pp. 334-341.
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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.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.",
keywords = "Advanced glycation end products, age-related pathology, docosahexaenoic acid, microvasculature, N(epsilon)-(carboxymethyl)lysine (CML)",
author = "Fuijkschot, {Wessel W.} and {de Graaff}, {Hjalmar J.} and Ekatarina Berishvili and Zurab Kakabadze and Koba Kupreishvili and Elisa Meinster and Maaike Houtman and {van Broekhoven}, Amber and Schalkwijk, {Casper G.} and Vonk, {Alexander B. A.} and Krijnen, {Paul A. J.} and Smulders, {Yvo M.} and Niessen, {Hans W. N.}",
note = "{\circledC} 2016 Stichting European Society for Clinical Investigation Journal Foundation.",
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volume = "46",
pages = "334--341",
journal = "European Journal of Clinical Investigation",
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Fuijkschot, WW, de Graaff, HJ, Berishvili, E, Kakabadze, Z, Kupreishvili, K, Meinster, E, Houtman, M, van Broekhoven, A, Schalkwijk, CG, Vonk, ABA, Krijnen, PAJ, Smulders, YM & Niessen, HWN 2016, 'Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature' European Journal of Clinical Investigation, vol. 46, no. 4, pp. 334-341. https://doi.org/10.1111/eci.12599

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

In: European Journal of Clinical Investigation, Vol. 46, No. 4, 04.2016, p. 334-341.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature

AU - Fuijkschot, Wessel W.

AU - de Graaff, Hjalmar J.

AU - Berishvili, Ekatarina

AU - Kakabadze, Zurab

AU - Kupreishvili, Koba

AU - Meinster, Elisa

AU - Houtman, Maaike

AU - van Broekhoven, Amber

AU - Schalkwijk, Casper G.

AU - Vonk, Alexander B. A.

AU - Krijnen, Paul A. J.

AU - Smulders, Yvo M.

AU - Niessen, Hans W. N.

N1 - © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Advanced glycation end products

KW - age-related pathology

KW - docosahexaenoic acid

KW - microvasculature

KW - N(epsilon)-(carboxymethyl)lysine (CML)

U2 - 10.1111/eci.12599

DO - 10.1111/eci.12599

M3 - Article

VL - 46

SP - 334

EP - 341

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 4

ER -