scholarly journals ALKBH5 Exacerbates Aortic Dissection by Promoting Inflammatory Response and Apoptosis of Aortic Smooth Muscle Cells via Regulating lnc-TMPO-AS1/EZH2/IRAK4 Signals in an m6A Modification Manner

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Peng Wang ◽  
Min Zhang ◽  
Zhiwei Wang ◽  
Qi Wu ◽  
Feng Shi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Aortic Dissection ◽  
Smooth Muscle Cells ◽  
Noncoding Rna ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Downstream Target

Recently, mounting evidence indicates that N6-methyladenosine (m6A) modification functions as a pivotal posttranscriptional modification that regulates noncoding RNA biogenesis to influence the progression of multiple diseases. However, whether m6A modification is involved in aortic dissection (AD) development has never been reported. Meanwhile, numerous studies have shown that AngII-induced inflammatory damage and excessive apoptosis of human aortic smooth muscle cells (HASMCs) are the crucial pathological features of AD development. Therefore, in this study, we intended to explore whether m6A modification can regulate AD progression by influencing the damage effects of AngII on HASMCs and elucidate the underlying mechanisms. Firstly, we screened and confirmed the high expression of alkylation repair homolog protein 5 (ALKBH5), a key m6A demethylase, in aortic tissues from AD patients, indicating that m6A modification may indeed be involved in AD progression. Subsequently, we demonstrated that ALKBH5 can exacerbate the AngII-induced HASMC inflammatory injury as well as apoptosis and shorten the survival time of AngII-infused mice. Mechanistically, we revealed that lncRNA TMPO-AS1 is a downstream target for ALKBH5 to affect AD progression in vitro and vivo. Meanwhile, we confirmed that ALKBH5-mediated m6A demethylation downregulates lnc-TMPO-AS1 by decreasing the stability of its nascent. Further, we demonstrated that lnc-TMPO-AS1 exhibits its functions in HASMCs, at least partly, through downregulating IRAK4 at the epigenetic level by combining with EZH2. Finally, the direct positive correlation between ALKBH5 and IRAK4 in terms of the expression level and biological function was confirmed, which further enforced the preciseness and correctness of our findings. In conclusion, our study demonstrated that ALKBH5 aggravates AD by promoting inflammatory response and apoptosis of HASMCs via regulating lnc-TMPO-AS1/EZH2/IRAK4 signals in an m6A modification manner and may provide a novel molecular basis for subsequent researchers to searching for novel therapeutic approaches to improve the health of patients fighting AD and other cardiovascular diseases.

Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Smooth Muscle Cells ◽  
Adhesion Molecule ◽  
Vascular Inflammation ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Tnf Α ◽  
Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

Density-dependent hyperpolarization in cultured aortic smooth muscle cells

1989 ◽  
Vol 256 (3) ◽  
pp. C644-C651 ◽  
Author(s):  
M. G. Blennerhassett ◽  
M. S. Kannan ◽  
R. E. Garfield
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Continuous Process ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Sprague Dawley ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Wistar Kyoto

The membrane potential (Em) of cultured aortic smooth muscle cells from Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats was measured in proliferating primary cultures. Em of SD cells in high-density cultures was -51 to -58 mV, whereas that of low-density cultures (1-2 days) was -30 mV. This difference was due to a continuous process of hyperpolarization during proliferation in culture. Em of WKY and SHR hyperpolarized similarly, from -12 to -42 and -38 mV, respectively. Hyperpolarization of Em of SD, WKY, and SHR cells was related to cell density rather than time in culture. Em may be a sensitive and significant indicator of the changes in the differentiated state expressed by proliferating smooth muscle in vitro.

Atorvastatin limits the pro-inflammatory response of rat aortic smooth muscle cells to thrombin

2003 ◽  
Vol 474 (2-3) ◽  
pp. 175-184 ◽  
Author(s):  
Mounsif Haloui ◽  
Olivier Meilhac ◽  
Martine Jandrot-Perrus ◽  
Jean-Baptiste Michel
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

scholarly journals Unusual lysosomes in aortic smooth muscle cells: presence in living and rapidly frozen cells.

1986 ◽  
Vol 102 (5) ◽  
pp. 1615-1622 ◽  
Author(s):  
J M Robinson ◽  
T Okada ◽  
J J Castellot ◽  
M J Karnovsky
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Lucifer Yellow ◽  
Muscle Cells ◽  
Rapid Freezing ◽  
Tubular Structures ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Ultrastructural Appearance

Unusual tubular structures have been observed in rat aortic smooth muscle cells (SMC) grown in culture. These tubular structures have several characteristics that strongly suggest that they are lysosomes: they are bounded by a single membrane bilayer, contain densely staining material, and acid phosphatase activity. Furthermore, these structures are present in living cells, as demonstrated by their ability to accumulate the membrane-impermeable fluorescent dye lucifer yellow CH. In ultrastructural preparations they are best seen in samples that are cryofixed by rapid freezing and then freeze-substituted in osmium-acetone solutions. Conventional chemical fixation did not appear to preserve these structures to as great an extent as did rapid freezing. Comparison of SMC in vitro to the same cells in situ revealed differences in lysosome number as well as morphological appearance. Thus, the culturing of rat SMC leads to the formation of unusual tubular lysosomes whose ultrastructural appearance is particularly sensitive to the methods employed for examination.

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