Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis.

Description

The investigators examined the effects of recombinant apolipoprotein-A-I (Milano) (ETC-216) on plaque vulnerability of New Zealand White rabbits with advanced aortic lesions. Animals were randomized to receive two doses of ETC-216 (75mg/kg) 4 days apart or vehicle. Plaque size (6%), as quantified by magnetic resonance imaging, was significantly reduced in rabbits treated with ETC-216. This change was associated with lower plaque macrophage density and with a downregulation of gene and protein expression of tissue factor, monocyte chemoattractant protein-1, and cyclooxygenase-2, while cyclooxygenase-1 seemed to be upregulated. These results suggest that short-term administration of apoA-1 (Milano) has several benefits on plaque vulnerability in these experimental models of atherosclerosis. The paper was accompanied by an editorial by Zhao and Brown who were not entirely convinced that the 6% reduction in plaque size would have significant biological or clinical benefits. They also questioned the experimental model used, noting that the plaque morphology of rabbits is somewhat different from that of humans, in that it is more easily lipid depleted. This difference would likely affect whether study findings could be repeated in clinical practice. The high cost and potential inconvenience of using apoA-1 (Milano) in clinical practice was also addressed.