Increased retention of LDL from type 1 diabetic patients in atherosclerosis-prone areas of the murine arterial wall. (July 2019)

• Record Type: Journal Article
• Authors: Hagensen, Mette K.; Mortensen, Martin B.; Kjolby, Mads; Palmfeldt, Johan; Bentzon, Jacob F.; Gregersen, Soeren
• Is Part Of: Atherosclerosis. Volume 286(2019)
• Page Start: 156
• Page End: 162
• Publication Date: 2019-07
• Subjects: Type 1 diabetes -- Atherosclerosis -- Low density lipoprotein -- Retention; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2019.02.027
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: LDL from patients with type 1 diabetes showed higher retention at atherosclerosis-prone sites in the arterial wall. Extensive glycation of LDL in vitro increased its retention in the arterial wall in vivo compared with nonglycated LDL. LDL particle size does not explain the increased arterial retention of LDL from type 1 diabetic subjects. Using LC-MS/MS, we identified four previously unrecognized sites of glycation in vitro within the protein sequence of apoB.