Agerelated increase in LDLcholesterol is associa

Authors: Saem Jung Minjoo Kim Hyo Jeong Ryu Jey Sook Chae SangHyun Lee Jong Ho Lee

Publish Date: 2014/05/11

Volume: 11, Issue: 1, Pages: 40-49

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Abstract

We investigated alterations in plasma metabolites associated with the agerelated increase in circulating concentration of lowdensity lipoprotein LDLcholesterol The study included 602 healthy nondiabetic subjects aged 30–65 years Among 393 individuals with LDLcholesterol within the normal limit at baseline 56 142  developed high fasting LDLcholesterol levels after 3 years The 337 subjects that retained normal LDLcholesterol were matched for age gender BMI and fasting LDLcholesterol to form the control group n = 78 At the 3year followup the highLDL group showed greater increases in serum totalcholesterol and LDLcholesterol plasma oxidized LDL lipoproteinassociated phospholipase A2 activity and urinary 8epiprostaglandin F2α than the control group after adjusting for baseline levels The highLDL group also showed significant decreases in sphingomyelin SM d180/161 and phosphatidylcholine PC 180/204 which were associated with an increases on LDLcholesterol and significant increases in palmitic amide and lactosylceramide Mean changes in the levels of SM d180/161 C17 sphinganine PC 180/204 and eight lysoPCs containing C161 C160 C170 C181 C180 C204 C203 and C226 were statistically different between control and highLDL groups Overall the change in oxLDL positively correlated with changes in LDLcholesterol LpPLA2 activity palmitic amide oleamide lysoPCs and C17 sphinganine and negatively correlated with changes in SM d180/161 r = −0501 P  0001 An agerelated increase in LDLcholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolismSample collection and experiments were performed by S J M K H J R J S C SH L and J H L Data were analyzed by S J M K and J H L J H L provided the research funding and S J M K and J H L wrote the manuscript All of the authors read commented on and contributed to the submitted manuscript No potential conflicts of interest relevant to this article were reported The authors thank the research volunteers who participated in the studies described in this article and the technical assistants of Yonsei Center for Research Facilities Yonsei University for data generation of LC–MS LTQ Orbitrap microLC This research was supported by the Bio and Medical Technology Development Program NRF20062005306 and NRF2012M3A9C4048762 and Midcareer Researcher Program NRF20100015017 of the National Research Foundation NRF funded by the Ministry of Science ICT Future Planning Republic of KoreaAll procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation institutional and national and with the Helsinki Declaration of 1975 as revised in 2000 Informed consent was obtained from all participants for being included in the study

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