Constant Light Exerted Detrimental Cardiovascular Effects Through Sympathetic Hyperactivity in Normal and Heart Failure Rats.

It has been documented that constant light exposure exerts complicated cardiovascular effects. However, a mounting collection of conflicting results did not make it any easier for researchers and physicians to consider the role of light on cardiovascular function. This study was designed to investigate how constant light exposure (24 h light/day) influences the cardiac function in normal and heart-failure (HF) rats. In normal rats, two groups of SD rats were accustomed in 12 h light/12 h dark (LD) or 24 h light (constant light, CL) for 4 weeks. In HF rats which was induced by myocardial infarction (MI) was let recover in LD for 4 weeks. Interestingly, compared with rats in LD environment (ejection fraction, EF%: 93.64 ± 2.02 in LD, 14.62 ± 1.53 in HF-LD), constant light (2 weeks) weakened the cardiac function in normal and HF rats (EF%: 79.42 ± 2.91 in CL, 11.50 ± 1.08 in HF-CL). The levels of renal sympathetic nerve activity and c-fos expression in the rostral ventrolateral medulla (RVLM), a key region controlling sympathetic outflow, were significantly increased in normal and HF rats after constant light (RSNA, Max%: 8.64 ± 0.48 in LD, 20.02 ± 1.24 in CL, 20.10 ± 1.16 in HF-LD, 26.82 ± 1.69 in HF-CL). In conclusion, it is suggested that constant light exposure exerts detrimental cardiovascular effects, which may be associated with the RVLM-related sympathetic hyperactivity.

[SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats].

OBJECTIVE: To investigate the effects of ß3-adrenoceptors(ß3-AR) inhibitor SR 59230A on MicroRNAs expression in rat myocardium with chronic heart failure and the related mechanisms. METHODS: One hundred male SD rats were randomly divided into sham operated group(40)and chronic heart failure(CHF)group(60). Coronary artery ligation was used to induce CHF. Then the rats in CHF group were further randomly divided into CHF control group and CHF+SR 59230A group (CHF+SR). Rats in the sham group were divided into sham control group and sham+SR 59230A group (Sham+SR). The rats in Sham+SR group and CHF+SR group were treated with 1 ml SR 59230A(85 mmoL/L in 0.9% saline)twice a day for seven weeks by intraperitoneal injection, while the rats in control groups were injected with the same amount of saline for seven weeks separately. miScript miRNA PCR Arrays were used to determine the expression profile of MicroRNAs. Immunohistochemistry was used to evaluate the distribution of the related proteins in the heart tissue sections. Western blot was used to detect the expressions of nuclear factor-kappaB(NF-κB),p53 and p53-Phospho-Serine 15 in the heart. RESULTS: ①After in vivo blockade of ß3-AR by SR 59230A, there were 18MicroRNAs down-regulated in sham control group and CHF control group. Within them, 6 MicroRNAs were related to NF-κB signaling pathway, they were miR-125b-5p,miR-143-3p,miR-145-5p,miR-26a-5p,miR-30a-5p and miR-320-5p. ②Slides from the heart tissue showed that NF-κB was distributed both in nucleus and cytoplasm, while p53 in cytoplasm was more than that in nucleus in heart tissue sections. The expressions of NF-κB and p53 were higher in the CHF control group than those in the sham control group(P<0.05), but were lower in CHF+SR group than those in CHF control group(P<0.05),while they were elevated in Sham+SR group compared to the sham control group(P<0.05). ③ Compared with the sham control group, the protein expression of NF-κB p65 was increased significantly in the CHF control group (P<0.05). After treated with SR59230A in vivo,the protein expressions of NF-κB and p53-Phospho-Serine 15 were decreased significantly in CHF rats(P<0.05),while the protein expressions of NF-κB, p53 and p53-Phospho-Serine 15 proteins were increased in the sham rats (P<0.05). CONCLUSIONS: Blocking of ß3-AR improved the damaged heart in CHF rats; ß3-AR caused the change of MicroRNAs expression, and it related to NF-κB signal pathway.

[Effect of ß3-AR antagonist SR59230A on the tension and microRNA expression of rat thoracic aorta].

OBJECTIVE: To explore the effects of SR59230A on the tension and microRNA (miRNA) expression of rat thoracic aorta. METHODS: Forty-four SD rats were used in the experiment. Twenty-four rats were used to observe the effect of SR on the tension of thoracic aortic rings. Another 20 rats were randomly divided into control (n=10) and SR group(n=10). Rats in SR group were injected SR intraperitoneally,and in control group were given 0.9% of saline. After 5 weeks, the blood pressure of all rats were measured. Then the tension to NA and the expression of miRNA of thoracic aorta rings were measured. RESULTS: (1) The tension of thoracic aortic rings responding to 30 mmol/LKCl were increased by pretreatment of SR (P<0.05); (2) After 5 weeks injection of SR, systolic pressure was increased (P<0.05); (3) The tension in SR group was increased in presence of 1 µmol/L and 10 µmol/L of NA (P<0.05,P<0.01). (4) After 5 weeks of SR in vivo application,18 miRNA were down-regulated, 7 of them had statistical significance, they were rno-miR-143-3p, rno-miR-29b-3p, rno-miR-31a-5p, rno-let-7b-5p, rno-miR-214-3p, rno-miR-222-3p and rno-miR-352; 11 miRNA were up-regulated, 4 of them had statistical significance, they were rno-miR-206-3p、rno-miR-223-3p、rno-miR-342-3p and rno-miR-499-5p respectively. CONCLUSIONS: SR59230A increased the tension of rat thoracic aorta. In vivo administration of SR led to increase of systolic pressure of rat,down-regulation of rno-miR-143-3p、rno-miR-29b-3p、rno-miR-31a-5p、rno-let-7b-5p、rno-miR-214-3p、rno-miR-222-3p、rno-miR-352 and up-regulation of rno-miR-206-3p、rno-miR-223-3p、rno-miR-342-3p and rno-miR-499-5p.

[Silencing of PKG1 expression enhances the efficacy of vemurafenib against melanoma cell].

OBJECTIVE: To explore whether targeting phosphoglycerate kinase 1 (PGK1) can enhance the sensitivity of BRAFV600E mutation melanoma cells to vemurafenib. METHODS: The methods of cell biology, molecular biology and pharmacology(MTT assay, Western blot, FCM, Colongenic assay) were used in this study. RESULTS: ① Silencing of PGK1 expression increased the efficacy of vemurafenib in melanoma cells, as evidenced by greater killing in the tumor cells subjected to combined treatment of vemurafenib with siPGK1; ②The mechanism of enhanced sensitivity of melanoma cells to vemurafenib was associated with activation of apoptotic signaling pathway. CONCLUSIONS: Targeting of PGK1 may represent a novel strategy of sensitizing melanoma cells to vemurafinib.