Paradis V, Mathurin P, Ratziu V, Poynard T, Bedossa P
Service d'Anatomie Pathologique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France.
Hepatology. 1996 May;23(5):1232-8. doi: 10.1053/jhep.1996.v23.pm0008621158.
Apolipoprotein A-I (Apo A-I), a protein produced mainly by hepatocytes, is decreased in the sera of alcoholic patients with liver fibrosis and cirrhosis. To explain this decrease, we investigated possible interactions 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 fibronectin (FN) (optical density [OD] = 1.11 +/- .26, P = .01) and collagen (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 negative correlation between Apo A-I and liver fibrosis is amplified in alcoholic patients, we investigated whether the in vitro formation of Apo A-I/acetaldehyde complex (adducts) increased the binding of Apo A-I to the ECM. We showed that the amount of Apo A-I that bound to FN was significantly higher with acetaldehyde-modified Apo A-I (OD = 2.18 +/- 0.19, P = .01) than with native Apo A-I. This increase was probably related to the formation and binding of Apo A-I dimers, because immunoblot of in vitro acetaldehyde-modified Apo A-I showed the formation of dimeric Apo A-I. In conclusion, FN binds both native and acetaldehyde-modified Apo A-I. Because FN is deposited early and in excess during liver fibrosis, a storage mechanism of Apo A-I on newly deposited fibronectin would explain, in part, the decrease observed in alcoholic patients with liver fibrosis.
载脂蛋白A-I（Apo A-I）主要由肝细胞产生，在患有肝纤维化和肝硬化的酒精性肝病患者血清中含量降低。为解释这种降低现象，我们研究了肝细胞外基质（ECM）与Apo A-I之间可能存在的相互作用。采用固相结合试验，我们评估了Apo A-I与不同肝基质成分的结合情况。与牛血清白蛋白（BSA）（光密度[OD]=0.26±0.16）相比，Apo A-I与纤连蛋白（FN）（OD = 1.11±0.26，P = 0.01）和I型胶原（C）（OD = 0.91±0.22，P = 0.02）有显著结合。Apo A-I与纤连蛋白的结合呈浓度依赖性且具有饱和性。Apo A-I在体内也与ECM结合，因为在酒精性肝病患者肝活检标本的纤维间隔上通过免疫荧光检测到了Apo A-I。由于酒精性肝病患者中Apo A-I与肝纤维化之间的负相关关系更为明显，我们研究了体外形成的Apo A-I/乙醛复合物（加合物）是否会增加Apo A-I与ECM的结合。我们发现，与天然Apo A-I相比，乙醛修饰的Apo A-I与FN结合的量显著更高（OD = 2.18±0.19，P = 0.01）。这种增加可能与Apo A-I二聚体的形成和结合有关，因为体外乙醛修饰的Apo A-I的免疫印迹显示形成了二聚体Apo A-I。总之，FN既能结合天然Apo A-I，也能结合乙醛修饰的Apo A-I。由于FN在肝纤维化早期过量沉积，Apo A-I在新沉积的纤连蛋白上的储存机制可以部分解释酒精性肝病患者中观察到的Apo A-I降低现象。
