BINDING OF APOLIPOPROTEIN-A-I AND ACETALDEHYDE-MODIFIED APOLIPOPROTEIN-A-I TO LIVER EXTRACELLULAR-MATRIX

Apolipoprotein A-I (Ape A-I), a protein produced mainly by hepatocytes , is decreased in the sera of alcoholic patients with liver fibrosis a nd cirrhosis. To explain this decrease, we investigated possible inter actions between liver extracellular matrix (ECM) and Apo A-I. Using a solid-phase binding assay, we evaluated the binding of Apo A-I to the different liver matrix components. Apo A-I bound significantly to fibr onectin (FN) (optical density [OD] = 1.11 +/- .26, P = .01) and collag en (C) I (OD = 0.91 +/- 0.22, P = .02) in comparison with bovine serum albumin (BSA) (OD = 0.26 +/- 0.16). Binding of Apo A-I to fibronectin was concentration dependent and saturable. Apo A-I bound also to ECM in vivo because Apo A-I was detected by immunofluorescence on fibrous septa in liver biopsy specimens of alcoholic patients. Because a negat ive correlation between Apo A-I and liver fibrosis is amplified in alc oholic patients, we investigated whether the in vitro formation of Apo A-I/acetaldehyde complex (adducts) increased the binding of Apo AI to the ECM. We showed that the amount of Apo AI that bound to PN was sig nificantly higher with acetaldehyde-modified Apo A-I (OD = 2.18 +/- 0. 19, P = .01) than with native Apo A-I. This increase was probably rela ted to the formation and binding of Apo A-I dimers, because immunoblot of in vitro acetaldehyde-modified Apo A-I showed the formation of dim eric Apo A-I. In conclusion, FN binds both native and acetaldehyde-mod ified Apo A-I. Because FN is deposited early and in excess during live r fibrosis, a storage mechanism of Apo A-I on newly deposited fibronec tin would explain, in part, the decrease observed in alcoholic patient s with liver fibrosis.