Abstract 1355: The Impact of Glycation on the Anti-inflammatory Properties of High Density Lipoproteins in vivo
Background and Aims: High density lipoproteins (HDL) are potent inhibitors of vascular inflammation. Here we ask whether glycation of the main HDL protein (apoA-I), a known occurrence in diabetes, compromises these anti-inflammatory properties.
Methods: Human apoA-I was used either unmodified or after being chemically glycated to an extent comparable to that observed in diabetics. Acute inflammation was induced in normocholesterolemic rabbits (n=5/group) by inserting a non-occlusive collar around a carotid artery. 24h before collar insertion, animals received an iv infusion of:
unmodified lipid-free apoA-I,
glycated lipid-free apoA-I,
reconstituted HDL (rHDL) containing phosphatidylcholine (PC) and unmodified apoA-I or (v) rHDL containing PC and glycated apoA-I.
Infusions contained 8 mg/Kg apoA-I. Animals were sacrificed 24 h after collar insertion. Arterial inflammation was quantitated immunohistochemically.
Results: The carotid collar induced substantial infiltration of neutrophils into the artery wall and expression of VCAM-1 and ICAM-1 in the endothelium. Infusion of unmodified apoA-I reduced neutrophil infiltration by 89±1% and expression of VCAM-1 by 90±3% and ICAM-1 by 66±2% (all p<0.0001). These anti-inflammatory effects were significantly less when glycated apoA-I was infused, with neutrophil infiltration, VCAM-1 expression and ICAM-1 expression being reduced by 53±1%, 13±4% and 0%, respectively (all significantly less than with unmodified apoA-I, p<0.001). Infusion of rHDL containing unmodified apoA-I decreased neutrophil infiltration by 77±1%, (p<0.0001), VCAM-1 expression by 88±3% (p<0.0001) and ICAM-1 by 57±2% (p<0.001). These effects were significantly less after infuson with rHDL containing glycated apoA-I, with neutrophil infiltration, VCAM-1 expression and ICAM-1 expression being inhibited by 53±2%, 48±4% and 0%, respectively (all significantly less than with rHDL containing unmodified apoA-I, p<0.05).
Conclusion: Glycation of apoA-I (as found in diabetes) compromises the anti-inflammatory properties of HDL. This may contribute to the high susceptibility of diabetic subjects to vascular disease.