| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5948851 | Atherosclerosis | 2012 | 6 Pages |
ObjectivesHigh 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.Methods and resultsWe 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.ConclusionsThe 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.
⺠Subjects with low HDL2 show LDL with high affinity for arterial proteoglycans (PG). ⺠HDL2 was a better inhibitor of LDL-PG association than HDL3. ⺠The athero-protective property of HDL2 may linked to its content of apoE. ⺠The protective capacity of HDL2 may be related to inhibition of LDL-PG association.
