Effect of Salusin-ß on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

Abstract

Background/Aims: salusin-ß is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-ß has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-ß on PPARγ gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. Results: Salusin-ß negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-ß on PPARγ gene expression contributed to salusin-ß-induced VSMCs proliferation and inflammation in vitro. IγBa-NF-γB activation, but not NF-γB p50 or p65, mediated the salusin-ß-induced inhibition of PPARγ gene expression. Salusin-ß induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-ß-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-ß was significantly reversed by an IγBa inhibitor BAY 11-7085. Furthermore, IγBa-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-ß treatment. Conclusion: IγBa-HDAC3 pathway may contribute to salusin-ß-induced inhibition of PPARγ gene expression in VSMCs.

The Association of Circulating MiR-29b and Interleukin-6 with Subclinical Atherosclerosis

“…Interestingly, Bacchiega et al found that the IL-6-blocking agent tocilizumab significantly reduced CRP concentrations, together with parameters of systemic inflammation [26]. IL-6 has many other functions, including activation of macrophages [27, 28] and stimulation of endothelial [29, 30] and vascular smooth muscle cells [31, 32]. Although IL-6 and miR-29b both have a number of clear effects on different stages in the formation of atherosclerosis and are, individually, important markers for CVD, we have shown that that the combination of miR-29b and IL-6 offers a better predictive marker for atherosclerosis than either miR-29b or IL-6 alone.…”

Fibrinopeptide A Induces Expression of C-Reactive Protein via the ROS-ERK1/2/ P38-NF-κB Signal Pathway in Vascular Smooth Muscle Cells

“…The primary VSMCs separated from the thoracic aorta of male Sprague Dawley (SD) rats were cultured in DMEM supplemented with 10% FBS, 100 U/ml penicillin and 100 U/ml streptomycin at 37℃ in a 5% CO 2 incubator as previously described [30, 31]. The cells showed the typical “hill and valley” morphology and 99% purity as identified by the immunofluorescence staining with α -smooth muscle-actin antibody (showed in Fig.…”

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