Abstract 19253: Acute Inflammation Following Dental Treatment Alters Endothelial Effects, but not Cholesterol Efflux Capacity of HDL

Abstract

Background:HDL elevating therapies have thus far failed to improve CV outcome and the loss of anti-atherosclerotic properties of HDL has recently been reported in CAD. This suggests specific biological activities of HDL, rather than its cholesterol content, may be crucial in mediating the anti-atherogenic effects of HDL.

Aim: To determine the impact of acute systemic inflammation on various measures of HDL function.

Methods: 50 subjects with periodontitis (PD) (Age 49.8 [6.5]) underwent dental treatment. In vivo changes in endothelial function were determined using Flow Mediated Dilatation (FMD). HDL function was assayed at baseline, at the peak of the inflammatory response (24 hours after PD treatment) and following resolution (6 months post PD treatment). HDL-mediated cholesterol efflux was measured in J774 macrophage cells, pre-treated with cAMP. Impact of HDL on cultured endothelial aortic cells was assayed by measuring HDL-dependent Nitric Oxide bioavailibility (NO) and superoxide (SO) production using ESR Spectroscopy. HDL-associated Paraoxonasae-1 (PON1) activity was measured by spectrophotometry.

Results and Discussion: 24 hours after dental treatment HDL became dysfunctional, as shown by reduced NO and increased SO production by cultured endothelial cells (P<0.01 for both). In addition, PON1 activity was reduced (P=<0.05), but no difference was found in cholesterol efflux capacity. At 6 months, these changes in HDL function returned to baseline levels, whereas cholesterol efflux capacity remained unchanged. Endothelial effects of HDL tracked with changes in inflammatory markers and FMD.

Conclusion: HDL becomes dysfunctional during acute inflammation resulting in abnormal endothelial responses, in the absence of any change in efflux capacity. Furthermore, the acute impairment of HDL function is reversible upon resolution of inflammation and tracks changes in FMD. These results suggest HDL function may contribute to the vascular alterations observed during an inflammatory response and may represent a novel mechanism whereby inflammation may promote atherosclerosis, i.e. by altering the endothelial effects of HDL.