Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells.

BACKGROUND: Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT). METHODS: HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis. RESULTS: Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 µM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice. CONCLUSIONS: DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.

Association between plasma macrophage migration inhibitory factor concentration and coronary artery lesion severity / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the plasma macrophage migration inhibitory factor (MIF), activator protein-1 (AP-1) and MMP-9 concentrations and the severity of coronary artery lesions in coronary heart disease (CHD) patients.</p><p><b>METHODS</b>Patients were divided into normal controls (n = 35), stable angina pectoris (SAP, n = 32) and acute coronary syndrome (ACS, n = 75) according to the coronary angiography (CAG), clinical and laboratory examinations. The CAG severity and extent of coronary lesions were analyzed by means of Gensini coronary score system. Enzyme linked immunosorent assay was used to measure the plasma MIF, AP-1 and MMP-9 concentrations.</p><p><b>RESULTS</b>Plasma MIF, AP-1 and MMP-9 concentrations were significant increased in CHD patients [MIF: (14.97 +/- 2.11) microg/L, AP-1: 1.43 +/- 0.33, MMP-9: (1.48 +/- 0.14) microg/L] compared to those in control group [MIF: (9.07 +/- 1.28) microg/L, AP-1: 0.71 +/- 0.13, MMP-9: (1.01 +/- 0.07) microg/L, all P < 0.05]. The MIF, AP-1 and MMP-9 concentrations in ACS group [MIF: (16.66 +/- 2.56) microg/L, AP-1: 1.56 +/- 0.22, MMP-9: (1.58 +/- 0.14) microg/L] were also significant higher than those in SAP group [MIF: (11.01 +/- 2.12) microg/L, AP-1: 1.04 +/- 0.25, MMP-9: (1.25 +/- 0.07) microg/L, all P < 0.05] and there was significant positive correlation between MIF, AP-1 and MMP-9 concentrations and the Gensini score of coronary artery lesions (all P < 0.05). AP-1 was positively correlated with MMP-9 in CHD patients (P < 0.05).</p><p><b>CONCLUSIONS</b>Plasma MIF, AP-1 and MMP-9 concentrations were positively correlated to the severity of coronary lesions in CHD patients. Higher MIF, AP-1 and MMP-9 concentrations in ACS patients than in SAP patients might suggest higher plaque instability in ACS patients.</p>