Haptoglobin binds the anti-atherogenic protein Apolipoprotein E: impairment of the apolipoprotein E stimulation on both the enzyme lecithin-cholesterol acyl-transferase activity and the cholesterol uptake by hepatocytes

Haptoglobin (Hpt) binds the Apolipoprotein A-I (ApoA-I), and impairs its stimulation on lecithin:cholesterol acyl-transferase (LCAT), an enzyme playing a major role in the reverse cholesterol transport (RCT). The Apolipoprotein E (ApoE), like ApoA-I, promotes different steps of RCT, including LCAT stimulation. ApoE contains aminoacid sequences which are homologous to the ApoA-I region bound by Hpt and involved in the interaction with LCAT. Therefore Hpt was expected to bind also ApoE, and inhibit the ApoE stimulatory effect on LCAT. Western Blotting and enzyme-linked immunosorbent assay experiments demonstrated that the Hpt subunit  actually binds ApoE. The Hpt affinity for ApoE was higher than that for ApoA-I. High ratios of Hpt with either apolipoprotein, as those associated with the acute phase of inflammation, inhibited in vitro ApoE in stimulating the cholesterol esterification activity of LCAT. Hpt also impaired human hepatoblastoma-derived cells in uptaking 3H-cholesterol from proteoliposomes containing ApoE or ApoA-I. We suggest that the interaction between Hpt and ApoE represents a mechanism by which inflammation affects atherosclerosis progression. Hpt might influence ApoE function in processes different from RCT.