Ethanol‐Induced Up‐Regulation of Candidate Plasminogen Receptor Annexin II in Cultured Human Endothelial Cells

Abstract

These results demonstrated that low ethanol increased Ann-II antigen/mRNA levels and up-regulated Ann-II gene expression at the transcriptional level. The results further identify and define the contribution and role of the plasminogen receptor, Ann-II, in the ethanol-induced mechanism of increased EC fibrinolysis that may underlie and contribute, in part, to the cardioprotective benefit associated with moderate alcohol consumption.

Direct effects of alcohol on hepatic fibrinolytic balance: Implications for alcoholic liver disease

“…ANXA2 was up-regulated in endothelial cells from cirrhotic ALD liver which is consistent with reports of ANXA2 over-expression in HUVEC cells in the presence of alcohol [12]. We found co-localization of ANXA2 with p11 (Fig.…”

“…ANXA2 is known to enhance plasmin generation and activation of clot dissolution in endothelial cells [9] and breast cancer cells [10]. A doubling of fibrinolytic activity with increased ANXA2 expression was reported at the surface of human vascular endothelial cells (HUVEC) on exposure to low levels of alcohol [11,12]. The cardioprotective role of low dose alcohol was thought to be mediated, at least in part, via potentiation of ANXA2 regulated fibrinolysis [11,12].…”

“…A doubling of fibrinolytic activity with increased ANXA2 expression was reported at the surface of human vascular endothelial cells (HUVEC) on exposure to low levels of alcohol [11,12]. The cardioprotective role of low dose alcohol was thought to be mediated, at least in part, via potentiation of ANXA2 regulated fibrinolysis [11,12]. ANXA2 is known to increase fibrinolysis in various cells and mediates plasminogen-dependent matrix invasion [5,13] that was inhibited with anti-ANXA2 antibody [13,14].…”

Intrahepatic gene expression in human alcoholic hepatitis

“…Alcohol induced up-regulation of annexin A2 was reported in endothelial cells [24]. Over-expression of annexin A2 and p11 in the liver in response to alcohol may regulate the production and degradation of plasmin and could modulate fibrinolysis, ECM degradation and fibrosis in ALD.…”

Alcohol‐Induced Up‐Regulation of Fibrinolytic Activity and Plasminogen Activators in Human Monocytes

“…Similarly, Miyamoto et al (1999) demonstrated that alcohol augmented isoproterenol-stimulated t-PA gene expression and decreased PAI-1 messenger RNA (mRNA) levels in cultured human ECs. In concert, these alcohol-induced changes in fibrinolytic components result in increased fibrinolysis (Aikens et al, 1998;Tabengwa et al, 2000).…”