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

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.

• Publication year

  2019

• Venue

  Atherosclerosis

• Publication date

  2019-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.atherosclerosis.2019.02.027PMID 30871723
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths

  2018cited by this paper
• Type 1 diabetes increases retention of low-density lipoprotein in the atherosclerosis-prone area of the murine aorta.

  2017cited by this paper
• NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells

  2016cited by this paper
• Glycated apolipoprotein B-A surrogate marker of subclinical atherosclerosis.

  2016cited by this paper
• The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity

  2016cited by this paper
• Quantitative assessment of methyl‐esterification and other side reactions in a standard propionylation protocol for detection of histone modifications

  2016cited by this paper
• Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

  2015cited by this paper
• Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association.

  2014cited by this paper
• Ceramides Contained in LDL Are Elevated in Type 2 Diabetes and Promote Inflammation and Skeletal Muscle Insulin Resistance

  2013cited by this paper
• Prevention of TGFβ induction attenuates angII-stimulated vascular biglycan and atherosclerosis in Ldlr−/− mice1[S]

  2013cited by this paper
• A Mendelian Randomization Study

  2012cited by this paper
• Glycation of LDL by Methylglyoxal Increases Arterial Atherogenicity

  2011cited by this paper
• Increased risk of cardiovascular disease in Type 1 diabetes: arterial exposure to remnant lipoproteins leads to enhanced deposition of cholesterol and binding to glycated extracellular matrix proteoglycans

  2011cited by this paper
• Increased Glycation and Oxidative Damage to Apolipoprotein B100 of LDL Cholesterol in Patients With Type 2 Diabetes and Effect of Metformin

  2010cited by this paper
• Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development11 This work was presented in part at the Arteriosclerosis, Thrombosis, and Vascular Biology annual conference, Denver, CO, 2006. Published, JLR Papers in Press, November 21, 2007.

  2008cited by this paper
• Acid Sphingomyelinase Promotes Lipoprotein Retention Within Early Atheromata and Accelerates Lesion Progression

  2008cited by this paper
• Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis.

  2008cited by this paper
• Heparan Sulfate in Perlecan Promotes Mouse Atherosclerosis: Roles in Lipid Permeability, Lipid Retention, and Smooth Muscle Cell Proliferation

  2008cited by this paper
• Retention of Low-Density Lipoprotein in Atherosclerotic Lesions of the Mouse: Evidence for a Role of Lipoprotein Lipase

  2007cited by this paper
• Effect of glycated LDL on microvascular tone in mice: a comparative study with LDL modified in vitro or isolated from diabetic patients

  2003cited by this paper
• Subendothelial retention of atherogenic lipoproteins in early atherosclerosis

  2002cited by this paper
• Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans.

  2002cited by this paper
• Induction of Rapid Atherogenesis by Perivascular Carotid Collar Placement in Apolipoprotein E–Deficient and Low-Density Lipoprotein Receptor–Deficient Mice

  2001cited by this paper
• Arterial intimal retention of pro-atherogenic lipoproteins in insulin deficient rabbits and rats.

  2000cited by this paper
• Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation.

  2000cited by this paper
• Glycation of plasma low density lipoproteins increases interaction with arterial proteoglycans.

  1999cited by this paper
• Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose.

  1999cited by this paper
• Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100.

  1998cited by this paper
• Epitopes close to the apolipoprotein B low density lipoprotein receptor-binding site are modified by advanced glycation end products.

  1998cited by this paper
• Chronic hyperglycemia increases arterial low-density lipoprotein metabolism and atherosclerosis in cynomolgus monkeys.

  1998cited by this paper
• Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding.

  1998cited by this paper
• Interaction of very-low-density, intermediate-density, and low-density lipoproteins with human arterial wall proteoglycans.

  1997cited by this paper
• Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.

  1996cited by this paper
• Nonenzymic glycation of apolipoprotein B in patients with insulin- and noninsulin-dependent diabetes mellitus.

  1995cited by this paper
• Isolation, Characterization, and Metabolism of the Glycated and Nonglycated Subfractions of Low-Density Lipoproteins Isolated from Type I Diabetic Patients and Nondiabetic Subjects

  1995cited by this paper
• Quantitative and Qualitative Lipoprotein Abnormalities in Diabetes Mellitus

  1992cited by this paper
• Comparison of Arterial Intimal Clearances of LDL from Diabetic and Nondiabetic Cholesterol‐fed Rabbits: Differences in Intimal Clearance Explained by Size Differences

  1989cited by this paper
• Turnover and tissue sites of degradation of glucosylated low density lipoprotein in normal and immunized rabbits.

  1987cited by this paper
• Glucosylation of Low-Density Lipoproteins to an Extent Comparable to That Seen in Diabetes Slows Their Catabolism

  1984cited by this paper
• Nonenzymatic Glucosylation of Low-Density Lipoprotein Alters Its Biologic Activity

  1982cited by this paper

• Vav3, a potential diagnostic and prognostic marker of diabetes, regulates glycolipid metabolism.

  2025cites this paper
• Apolipoprotein B-containing lipoproteins in atherogenesis

  2025cites this paper
• Trends and Disparities in Atherosclerotic Cardiovascular Disease Mortality in the Middle-Aged and Older Adults with Diabetes Mellitus in the United States, 1999-2019.

  2025cites this paper
• Adjunctive diabetes therapies and cardiovascular protection in type 1 diabetes: tackling the challenging Tchaikovsky piece.

  2025cites this paper
• Natural Products in Regulating Mitophagy for the Intervention of Atherosclerosis and Its Risk Factors: Mechanisms and Therapeutic Potential

  2025cites this paper
• Improved ASCVD Screening in Diabetes: a Focus on Scoring Models and Detection Techniques

  2025cites this paper
• Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease—Pathophysiology and Translational Therapeutic Approaches

  2023cites this paper
• Scavenger receptor a mediates glycated LDL transcytosis across endothelial cells to promote atherosclerosis.

  2023cites this paper
• Network pharmacology and molecular docking-based study on exploring the potential mechanism of Lycium barbarum L: In the treatment of atherosclerosis

  2023cites this paper
• Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives

  2023cites this paper
• Ultrasonic characteristics and influencing factors of atherosclerosis in diabetic patients.

  2022cites this paper
• Associations among carotid plaque progression, cerebrovascular/cardiovascular diseases and LDL-C/non-HDL-C goal achievement in diabetic patients: A retrospective cohort study.

  2022cites this paper
• Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

  2021cites this paper
• The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

  2020cites this paper
• The Role of Diabetes Mellitus (Both T1D and T2D) in the Atherosclerosis Development-A Systematic Review with Part of Inflammation along with Altered Glucose and Lipid Metabolism for Forming Therapeutic Approaches

  2020cites this paper
• Binding to heparin triggers deleterious structural and biochemical changes in human low-density lipoprotein, which are amplified in hyperglycemia.

  2020cites this paper
• Accelerated atherosclerotic cardiovascular risk in type 1 diabetes mellitus: Time for a new idea?

  2019cites this paper