2026-04-29T04:08:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/99462024-09-27T07:55:22Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Hagensen, Mette K
author
Mortensen, Martin B
author
Kjolby, Mads
author
Palmfeldt, Johan
author
Bentzon, Jacob F
author
Gregersen, Soeren
2020-05-07T10:49:13Z
2020-05-07T10:49:13Z
2019-07
Atherosclerosis. 2019; 286:156-162
0021-9150
http://hdl.handle.net/20.500.12105/9946
30871723
10.1016/j.atherosclerosis.2019.02.027
1879-1484
Atherosclerosis
BACKGROUND AND AIMS: Type 1 diabetes accelerates the development of atherosclerotic cardiovascular diseases. Retention of low-density lipoprotein (LDL) in the arterial wall is a causal step in atherogenesis, but it is unknown whether diabetes alters the propensity of LDL for retention. The present study investigated whether LDL from type 1 diabetic and healthy non-diabetic subjects differed in their ability to bind to the arterial wall in a type 1 diabetic mouse model. METHODS: Fluorescently-labeled LDL obtained from type 1 diabetic patients or healthy controls was injected into mice with type 1 diabetes. The amount of retained LDL in the atherosclerosis-prone inner curvature of the aortic arch was quantified by fluorescence microscopy. Healthy control LDL was in vitro glycated, analyzed for protein glycation by LC-MS/MS, and tested for retention propensity. RESULTS: Retention of LDL from type 1 diabetic patients was 4.35-fold higher compared to LDL from nondiabetic subjects. Nuclear magnetic resonance (NMR) spectroscopy analysis of LDL revealed no differences in the concentration of the atherogenic small dense LDL between type 1 diabetic and non-diabetic subjects. In vitro glycation of LDL from a non-diabetic subject increased retention compared to non-glycated LDL. LC-MS/MS revealed four new glycated spots in the protein sequence of ApoB of in vitro glycated LDL. CONCLUSIONS: LDL from type 1 diabetic patients showed increased retention at atherosclerosis-prone sites in the arterial wall of diabetic mice. Glycation of LDL is one modification that may increase retention, but other, yet unknown, mechanisms are also likely to contribute.
eng
Atherosclerosis
Low density lipoprotein
Retention
Type 1 diabetes
Increased retention of LDL from type 1 diabetic patients in atherosclerosis-prone areas of the murine arterial wall
journal article
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IncreasedRetentionOfLDL_2019.pdf
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IncreasedRetentionOfLDL_2019.pdf.txt