Reconstituted HDL lowers plaque lipids, macrophage size and measures of inflammation

Researchers from the Baker IDI Heart and Diabetes Institute, Melbourne, Australia showed that infusion of reconstituted high-density lipoprotein (rHDL) improved plaque characteristics, specifically lipid content, macrophage size and levels of inflammatory factors, in patients with peripheral vascular disease. This is the first in vivo study to show that treatment with rHDL can induce acute changes in plaque composition.

 

Shaw JA, Bobik A, Murphy A et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res 2008;103:1084-91.

 

In this exploratory study, 20 patients with symptom-limiting claudication were recruited. The mean age of patients was 68 years and over 50% had a history of coronary artery disease. All patients were on aspirin and almost all (18) were receiving statin therapy.  Statin therapy was then discontinued 1 week before the infusion. Patients with peripheral vascular disease were studied as the plaque from the superficial femoral artery provides a reasonable indication of what occurs in the coronary circulation.

 

Ten patients received rHDL 80 mg/kg given over 4 hours and the other half received a placebo infusion. The patients then underwent percutaneous superficial femoral artery revascularisation 5-7 days after the infusion, during which samples of plaque from the superficial femoral artery were obtained for histological staining and evaluation. Fasting blood samples were also taken before and 5-7 days after the infusion for measurement of lipid levels and inflammatory markers.

 

Plasma levels of HDL cholesterol in subjects treated with rHDL were increased by about 20% after the infusion compared with placebo (Figure 1). Interestingly, there were also increases of similar magnitude in plasma levels of low-density lipoprotein cholesterol and triglycerides (Figure 1). The authors explained that these findings were most likely a result of cessation of statin therapy prior to the infusion. The apolipoprotein B-depleted plasma was also able to support cholesterol efflux to a greater extent.

 

 

Significant differences were also seen in the plaque of the group treated with rHDL. Compared with the placebo group, plaque from subjects in the rHDL-treated group contained less lipid (p<0.05). There was also reduction in macrophage size in the rHDL-treated group (349 mm2 vs. 832 mm2 in the placebo group, p<0.05), indicative of reduced lipid accumulation, as well as a decrease in total expression of vascular cell adhesion molecule 1 (28% vs. 50%, p<0.05).

 

In their conclusions, the authors suggested that these changes in plaque content may contribute to the cardioprotective effects of HDL. However, they also highlighted the need for further study to determine the duration of these effects, and outcomes studies to evaluate the clinical benefit of treatment with rHDL infusion. 


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