Activin A: a possible marker for liver transplant outcome.

Activin A, a homodimeric protein consisting of two ßA subunit, is a member of the transforming growth factor-beta (TGF-ß) superfamily. This protein is involved in different physiological process: regulation of pituitary gonadotrophin secretion, stimulation, of spermatogonial proliferation and induction of erythroid and mesoderm differentiation (De Bleser et al., 1997). Activin A is produced by different cell types, including hepatocytes; these cells also express specific membrane receptors (Xu et al., 1995). The binding between activin A and its receptors activate a “cascade” of events such as apoptosis in the centrolobular region, inhibition of DNA (Schwall et al., 1193) and increase of collagen I synthesis (Sugiyama et al., 1998). Activin A inhibits hepatocytes proliferation induced by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) in a dose-dependent manner. Furthermore, HGF or EGF stimulate the hepatocyte synthesis of activin A (Yasuda et al., 1993). Partial hepatectomy in rats is followed by a maximal expression of activin A after 24 h (Kogure et al., 1995). Several studies suggest that activin A may be involved in regulation of hepatocytes proliferation and represents a potential inhibitor of hepatic regeneration (Fausto et al., 1995). We designed the present study in order to analyze the serum activin A levels in patients receiving a liver transplant (n=6

SERUM AND TISSUE EXPRESSION OF ACTIVIN A IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER

Activins are growth factors involved in the control of cell proliferation and differentiation. Human breast tissues express immunoreactive activin subunits, and activin A is able to inhibit the replication of mammary cells in vitro. The aim of the present study was to evaluate 1) whether breast cancer expresses activin betaA subunit mRNA, 2) whether serum activin A levels are altered in postmenopausal women with breast cancer, and 3) how circulating activin A levels change after tumor removal. Four groups of women (n = 158) were enrolled for the present prospective study: two groups were composed of postmenopausal women with breast cancer (n = 74) or benign lesions (n = 15); the third was a control group composed of healthy postmenopausal women (n = 62); and the fourth group included healthy fertile women (n = 7) undergoing plastic surgery with removal of non-neoplastic mammary tissue. RT-PCR showed that betaA subunit mRNA was expressed in breast carcinoma, fibroadenoma, and normal mammary tissue, and the level of expression was higher in carcinoma than in normal tissue (P < 0.05). Dimeric activin A was detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic tissue (P < 0.01). In women with breast cancer, median serum activin A levels were significantly higher than in controls (P < 0.001). The high serum activin A levels in patients with breast cancer were not correlated with the presence of lymph node metastasis, tumor grade, or tumor diameter. After tumor excision, a significant decrease of activin A in the first and second postoperative days was observed (P < 0.01; Friedman's ANOVA). Conversely, activin A levels remained unchanged after plastic surgery in healthy women. The present results suggest that activin A is expressed and secreted in postmenopausal women with breast cancer. The pathophysiological and possible clinical implications of this finding remain to be investigated

Decreased plasma endogenous soluble RAGE, and enhanced adipokine secretion, oxidative stress and platelet/coagulative activation identify non-alcoholic fatty liver disease among patients with familial combined hyperlipidemia and/or metabolic syndrome

Objective: In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, hyperactivity of the ligand-receptor for advanced glycation-end-products (RAGE) pathway, as reflected by inadequate protective response by the endogenous secretory (es)RAGE, in concert with genetic predisposition, may identify those with NAFLD even before and regardless of MS. Methods: We cross-sectionally compared 60 patients with vs. 50 without NAFLD. Each group included patients with FCHL alone, MS alone, and FCHL plus MS. Results: NAFLD patients had significantly lower plasma esRAGE, IL-10 and adiponectin, and higher CD40 ligand, endogenous thrombin potential and oxidized LDL. The effects of MS plus FCHL were additive. The genotypic cluster including LOX-1 IVS4-14A plus ADIPO 45GG and 256 GT/GG plus IL-10 10-1082G, together with higher esRAGE levels highly discriminate FCHL and MS patients not developing NAFLD. Conclusions: Among FCHL or MS patients, noncarriers of the protective genotypic cluster, with lower esRAGE and higher degree of atherothrombotic abnormalities coincide with the diagnosis of NAFLD. This suggests an interplay between genotype, adipokine secretion, oxidative stress and platelet/coagulative activation, accelerating NAFLD occurrence as a proxy for cardiovascular diseas