17ß-estradiol regulates adenosine triphosphate-binding cassette transporters A1 expression via estrogen receptor A to increase macrophage cholesterol efflux.

The liver is the focus of research on the effects of estrogen on cholesterol metabolism. Few studies have investigated the effects of estrogen on macrophages despite the significance of cells in atherosclerosis. The purpose of this study is to examine the effect of estrogen on macrophage cholesterol efflux. Macrophage cholesterol efflux, oil red O staining, RT-qPCR, Western blotting analyses were used to determine cholesterol metabolize and the expressions of adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1) and ATP-binding cassette transporter A1 (ABCA1) in J774A.1 cells, and the effect of these treatments was compared to without adding 17ß-estradiol (E2). Gain and loss of estrogen receptor alpha (ERα), liver X receptor α (LXRα) were conducted to study interactions between E2, ERα, LXRα and ABCA. Finally, in mice, we validate the relationship between ERα and ABCA1. E2 increases cholesterol efflux from macrophages and decreases the formation of lipid droplets and positively regulates the expression of ABCA1. This suggests that estrogen receptors (ERs) directly regulate ABCA1 translation. We suppressed ERα, which decreased the mRNA and protein expression of ABCA1. At the mRNA level, E2 treatment could partially counteract these phenomena, but not at the protein level. ABCA1 expression decreased after LXRα was inhibited. This suggests that ABCA1 translation is directly regulated by ERα. In the ovariectomized mouse model of ABCA1 protein expression was significantly reduced in the peritoneal macrophages of the ovariectomy (OVX) group. ABCA1 protein expression was greater in the E2+OVX group than in the OVX group. E2 contributes to the positive regulation of ABCA1 expression and promotes cholesterol efflux in macrophages by binding to ERα. The effect is independent of ABCA1 transcription regulation by LXRα.

Effect of SERCA2a overexpression in the pericardium mediated by the AAV1 gene transfer on rapid atrial pacing in rabbits.

To study the effects of overexpression of the sarcoplasmic reticulum ATPase 2a (SERCA2a) gene on the activity and protein expression of SERCA2a after rapid atrial pacing (RAP) in New Zealand white rabbits. New Zealand white rabbits were randomly divided into a sham-operated group (group A), adeno-associated virus 1 (AAV1)/EGFP + atrial fibrillation (AF) model group (group B), or AVV1/SERCA2a + AF group (group C). The sham-operated group was used as a negative control. Each group consisted of 10 animals. Groups B and C were injected with 500 µL of the AAV1-EGFP reporter gene and 500 µL of the AAV1-SERCA2a target gene, respectively. Four weeks after AAV1-mediated gene transfer, the rabbits underwent 24 h of RAP to the right atrium. The animals were sacrificed and protein activity and protein expression in the myocardium were measured using the westernblot method. Four weeks after AAV1-mediated gene transfer, SERCA2a protein activity and expression were significantly higher in Group C than in Groups A and B (P < 0.05). RAP of the right atrium induced atrial fibrillation in rabbits, resulting in decreases in the activity and protein expression of SERCA2a. Pericardial AAV-1 mediated SERCA2a gene transfer resulted in the overexpression of SERCA2a, restoring SERCA2a activity and protein expression.

Relationship between the TaqI B polymorphism of the cholesterol ester transfer protein gene and atrial fibrillation in Han and Kazak populations.

The TaqI B polymorphism in the cholesterol ester transfer protein (CETP) (B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The B1 allele of the CETP gene is a known independent risk factor for genetic susceptibility to atrial fibrillation (AF); however, little is known about this polymorphism in the minority groups of Xinjiang, China. We examined the role of this polymorphism in AF using two independent case-control studies: the Han population (101 AF patients and 129 control subjects) and the Kazak population (103 AF patients and 101 control subjects). Carriers of the B1B1 genotype were more frequent among AF patients than among controls both in the Han population (34.7 versus 26.4%; χ(2) = 10.686, P = 0.001) and in the Kazak population (53.4 versus 24.8%; χ(2) = 27.802, P < 0.001). The odds ratio (OR) for carriers of the B1B1 genotype to AF susceptibility was 0.187 [95% confidence interval (CI) = 0.071- 0.491] in the Han group and 8.426 (95%CI = 2.295-30.933) in the Kazak population. After adjustment of confounding factors such as gender, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, and high-density lipoprotein, the difference remained significant in the Han group (P = 0.001; OR = 0.187, 95%CI = 0.071-0.491) and in the Kazak group (P = 0.001; OR = 8.426, 95%CI = 2.295-30.933). The presence of the B1B1 polymorphism of the Taq1B CETP genotype contributes to the development of AF in the Han and Kazak populations in western China (Xinjiang).