PMID- 25177914
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140902
LR  - 20220408
IS  - 2044-4052 (Print)
IS  - 2044-4052 (Electronic)
IS  - 2044-4052 (Linking)
VI  - 4
IP  - 9
DP  - 2014 Sep 1
TI  - Arginine-directed glycation and decreased HDL plasma concentration and 
      functionality.
PG  - e134
LID - 10.1038/nutd.2014.31 [doi]
AB  - BACKGROUND/OBJECTIVES: Decreased plasma concentration of high-density lipoprotein 
      cholesterol (HDL-C) is a risk factor linked to increased risk of cardiovascular 
      disease (CVD). Decreased anti-atherogenic properties of HDL are also implicated 
      in increased CVD risk. The cause is unknown but has been linked to impaired 
      glucose tolerance. The aim of this study was to quantify the modification of HDL 
      by methylglyoxal and related dicarbonyls in healthy people and patients with type 
      2 diabetes characterise structural, functional and physiological consequences of 
      the modification and predict the importance in high CVD risk groups. 
      SUBJECTS/METHODS: Major fractions of HDL, HDL2 and HDL3 were isolated from 
      healthy human subjects and patients with type 2 diabetes and fractions modified 
      by methylglyoxal and related dicarbonyl metabolites quantified. HDL2 and HDL3 
      were glycated by methylglyoxal to minimum extent in vitro and molecular, 
      functional and physiological characteristics were determined. A one-compartment 
      model of HDL plasma clearance was produced including formation and clearance of 
      dicarbonyl-modified HDL. RESULTS: HDL modified by methylglyoxal and related 
      dicarbonyl metabolites accounted for 2.6% HDL and increased to 4.5% in patients 
      with type 2 diabetes mellitus (T2DM). HDL2 and HDL3 were modified by 
      methylglyoxal to similar extents in vitro. Methylglyoxal modification induced 
      re-structuring of the HDL particles, decreasing stability and plasma half-life in 
      vivo. It occurred at sites of apolipoprotein A-1 in HDL linked to membrane 
      fusion, intramolecular bonding and ligand binding. Kinetic modelling of 
      methylglyoxal modification of HDL predicted a negative correlation of plasma 
      HDL-C with methylglyoxal-modified HDL. This was validated clinically. It also 
      predicted that dicarbonyl modification produces 2-6% decrease in total plasma HDL 
      and 5-13% decrease in functional HDL clinically. CONCLUSIONS: These results 
      suggest that methylglyoxal modification of HDL accelerates its degradation and 
      impairs its functionality in vivo, likely contributing to increased risk of 
      CVD-particularly in high CVD risk groups.
FAU - Godfrey, L
AU  - Godfrey L
AD  - Clinical Sciences Research Laboratories, Medical School, University of Warwick, 
      University Hospital, Coventry, UK.
FAU - Yamada-Fowler, N
AU  - Yamada-Fowler N
AD  - Clinical Sciences Research Laboratories, Medical School, University of Warwick, 
      University Hospital, Coventry, UK.
FAU - Smith, J
AU  - Smith J
AD  - Bruker UK Ltd, Banner Lane, Coventry, UK.
FAU - Thornalley, P J
AU  - Thornalley PJ
AD  - Clinical Sciences Research Laboratories, Medical School, University of Warwick, 
      University Hospital, Coventry, UK.
FAU - Rabbani, N
AU  - Rabbani N
AD  - Clinical Sciences Research Laboratories, Medical School, University of Warwick, 
      University Hospital, Coventry, UK.
LA  - eng
PT  - Journal Article
DEP - 20140901
PL  - England
TA  - Nutr Diabetes
JT  - Nutrition & diabetes
JID - 101566341
PMC - PMC4183972
EDAT- 2014/09/02 06:00
MHDA- 2014/09/02 06:01
PMCR- 2014/09/01
CRDT- 2014/09/02 06:00
PHST- 2014/04/05 00:00 [received]
PHST- 2014/07/06 00:00 [revised]
PHST- 2014/07/15 00:00 [accepted]
PHST- 2014/09/02 06:00 [entrez]
PHST- 2014/09/02 06:00 [pubmed]
PHST- 2014/09/02 06:01 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - nutd201431 [pii]
AID - 10.1038/nutd.2014.31 [doi]
PST - epublish
SO  - Nutr Diabetes. 2014 Sep 1;4(9):e134. doi: 10.1038/nutd.2014.31.