title: HDL2 interferes with LDL association with arterial proteoglycans: a possible athero-protective effect.
abstract: OBJECTIVE
  High levels of large HDL (HDL2) reduce cardiovascular disease risks apparently because it mediates reverse cholesterol transport, and it has anti-inflammatory properties. Here we explored the mechanism behind an additional athero-protective HDL effect related to its capacity to interfere with formation of insoluble LDL-proteoglycans associations, a key step in LDL entrapment in the intima and in atherogenesis.
  
  
  RESULTS
  We found that HDL2 levels from type 2 diabetes patients and controls are inversely correlated with complex formation between serum LDL and the arterial proteoglycans versican. Reconstitution experiments indicate that HDL2 was more efficacious inhibitor of the LDL-versican association than the smaller HDL3. This may explain why serum from patients with dyslipidemia of insulin resistance, with low levels of HDL2, have a higher capacity to form insoluble LDL-proteoglycan complex. ApoE enrichment of HDL2 and HDL3 or addition of copies of an apoE peptide with the proteoglycan-binding sequence of this apolipoprotein increased their inhibition of LDL-versican associations.
  
  
  CONCLUSIONS
  The inhibitory effect of HDL2 and HDL3 on LDL-versican associations was related to formation of apoE-mediated soluble HDL-versican complexes. We speculate that in the intima large, HDL2 subclasses, by forming reversible soluble associations with proteoglycans can compete with formation of irreversible LDL-proteoglycan aggregates. This can contribute to the HDL2 athero-protective effects. In the dyslipidemia of insulin resistance, associated with low levels of HDL2, this athero-protective property may be compromised.
authors.affiliation: AstraZeneca Cardiovascular Bioscience, Mölndal S-431 83, Sweden. mia.umaerus@astrazeneca.com
authors.forename: Mia
authors.initials: M
authors.lastname: Umaerus
authors.forename: Birgitta
authors.initials: B
authors.lastname: Rosengren
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Eva
authors.initials: E
authors.lastname: Hurt-Camejo
authors.forename: Germán
authors.initials: G
authors.lastname: Camejo
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D053439:Lipoproteins, HDL2 / Q000494:pharmacology*; D053440:Lipoproteins, HDL3 / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D053675:Versicans / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; C508322:VCAN protein, human; D053675:Versicans