Evidence map›Paper›PMID 22855737›Full record

ArticleJournal of lipid research2012

Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis.

Mengxiao Lu, Donald L Gantz, Haya Herscovitz, Olga Gursky

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Thermal Remodeling of Human HDL Particles Reveals Diverse Subspecies.Journal of the American Society for Mass Spectrometry · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Effects of triacylglycerol on the structural remodeling of human plasma very low- and low-density lipoproteins.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Mengxiao LuDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118. Electronic address: mxlu@bu.edu.
Donald L GantzDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
Haya HerscovitzDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
Olga GurskyDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118. Electronic address: gursky@bu.edu.
Boston University · US

Funding

STRUCTURE AND INTERACTIONS OF COMPLEX POLAR LIPIDSP01HL026335 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ATKINSON, DAVID · 1985 to 2010
$23.1M
Structural Thermodynamics of Human Apolipoprotein C-1R01GM067260 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GURSKY, OLGA · 2003 to 2024
$7.4M
NHLBI NIH HHS HL-026335NHLBI NIH HHS P01 HL026335NIGMS NIH HHS GM-067260NIGMS NIH HHS R01 GM067260
6 · The paper itself

Abstract

Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we showed that thermal denaturation mimics LDL remodeling and fusion, and revealed kinetic origin of LDL stability. Here we report the first quantitative analysis of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat denaturation, which is unique among lipoproteins, suggesting that fusion is preceded by other structural changes. High activation energy of denaturation, E(a) = 100 ± 8 kcal/mol, indicates disruption of extensive packing interactions in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and negative-stain electron microscopy suggest that LDL dimerization is an early step in thermally induced fusion. Monoclonal antibody binding suggests possible involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion accelerates at pH < 7, which may contribute to LDL retention in acidic atherosclerotic lesions. Fusion also accelerates upon increasing LDL concentration in near-physiologic range, which likely contributes to atherogenesis. Thermal stability of LDL decreases with increasing particle size, indicating that the pro-atherogenic properties of small dense LDL do not result from their enhanced fusion. Our work provides the first kinetic approach to measuring LDL stability and suggests that lipid-lowering therapies that reduce LDL concentration but increase the particle size may have opposite effects on LDL fusion.

Indexed as

AtherosclerosisChromatography, GelCircular DichroismHot TemperatureHumansHydrogen-Ion ConcentrationKineticsLipoproteins, LDLParticle SizeProtein DenaturationProtein StabilityLipoproteins, LDL

Identifiers

PMID22855737
PMCPMC3435550
OpenAlexW2165836751

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.