Prostaglandin F2alpha (PGF2alpha) plays a pivotal role in ovarian luteolysis by inhibiting the expression of steroidogenic acute regulatory (StAR) protein, leading to a decrease in intracellular cholesterol transport and luteal steroid production. Previously we have demonstrated that the transcription factor Yin Yang 1 (YY1) bound to three regions in the StAR promoter in vitro and repressed promoter activity. This study further defined the YY1-mediated PGF2alpha effect on the inhibition of StAR protein expression through YY1 interaction with a single region in the StAR promoter in vivo. PGF2alpha consistently suppressed StAR mRNA and protein expression in cultured luteal cells in a dose-dependent manner. PGF2alpha also enhanced YY1 protein expression and binding to its cis-element in a time-dependent pattern that preceded the decline in StAR protein levels. The StAR promoter region bound by YY1 was also associated with histone deacetylase 1 (HDAC1). PGF2alpha treatment promoted HDAC1 binding to and suppressed the histone H3 acetylation in this region. On the contrary, YY1 knockdown decreased HDAC1 binding, increased histone H3 acetylation, enhanced StAR protein expression, and negated PGF2alpha effect on StAR protein expression. Luciferase assays showed that YY1 overexpression inhibited StAR promoter activity and the addition of a HDAC inhibitor, trichostatin A, abrogated the effect of YY1. Trichostatin A-treated luteal cells displayed increased StAR protein expression. These data indicate that PGF2alpha enhances a direct YY1/StAR promoter interaction and the recruitment of HDAC1 to the promoter, thereby preventing transcriptional activation of the StAR gene.

Background/Aims: Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Little is known about the relationship between very low-density lipoprotein cholesterol (VLDL-C) and cardiovascular mortality in these patients. Methods: A total of 1324 incident patients who began continuous ambulatory peritoneal dialysis (CAPD) therapy at our hospital between January 1, 2005, and September 30, 2014, with baseline serum VLDL-C values were investigated. The associations of the VLDL-C levels with all-cause and cardiovascular mortality were assessed. Results: The mean age of the cohort was 50.2 ± 14.8 years, and the mean VLDL-C level was 33.6 ± 18.0 mg/dl. One hundred sixty-five (12.5%) patients died during the study period. Multivariable models revealed that the high VLDL-C group was associated with significantly higher all-cause (HR, 2.08, 95% CI, 1.13 to 3.29, P = 0.002) and cardiovascular mortality (HR, 1.92, 95% CI, 1.18 to 4.29, P = 0.013) compared with the low VLDL-C group even after adjusting for various covariates. Using the VLDL-C level as a continuous variable, the hazard ratios (HRs) of all-cause and cardiovascular mortality associated with a 10-mg/dl increase in VLDL-C level were 1.12 (95% CI, 1.02 to 1.26, P = 0.025) and 1.11 (95% CI, 1.02 to 1.22, P = 0.029), respectively. VLDL-C was associated more strongly to all-cause (e.g., Akaike information criteria of 1990.205 vs. 1994.451) and cardiovascular (e.g., Akaike information criteria of 984.146 vs. 985.634) mortality than triglyceride (TG) levels. Conclusions: An elevated VLDL-C level is an independent risk factor for all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.

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