The protective effect of HOXA5 on carotid atherosclerosis occurs by modulating the vascular smooth muscle cell phenotype

Jing, Yuchen; Gao, Bai; Han, Zhiyang; Xia, Lifang; Xin, Shijie

doi:10.1016/j.mce.2021.111366

Cited by 15 publications

(11 citation statements)

References 44 publications

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“…Reduced HOXA5 expression has been implicated in intimal hyperplasia and derailed angiogenesis [ 17 ]. HOXA5 downregulation also promotes proatherogenic gene expression, extracellular matrix modification, and integrin alterations [ 40 ]. Moreover, in the setting of HOXA5 deficiency, macrophage cells and VSMCs switch towards the proinflammatory M1 phenotype [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens

Mylonas

Sarantis

Kapelouzou

et al. 2022

JCM

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Aims: Inflammatory dysregulation of mechanosensitive developmental genes may be central to atherogenesis. In the present seven-week model, we utilized colchicine regimens to curtail aortic atherogenesis in New Zealand White rabbits. We also explored the effect of colchicine regimens on atheroprotective (Klotho, HOXA5, NOTCH1, and OCT4) and proatherogenic (HIF1a, SOX2, BMP4, and NANOG) genes. Methods: The control (n = 6) and group A (n = 6) received standard and cholesterol-enriched chow, respectively. Groups B (n = 8) and C (n = 8) were fed hypercholesterolemic diet and were treated with colchicine plus fenofibrate or N-acetylcysteine (NAC), respectively. Results: Group A developed significantly greater thoracic and abdominal aortic atherosclerosis compared to groups B (p < 0.001) and C (p < 0.001). Combining colchicine with NAC resulted in stronger atheroprotection both in the thoracic and the abdominal aorta. In group A thoracic aortas, Klotho was downregulated compared to controls (95% CI: 1.82–15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p < 0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (95% CI: −8.09 to −0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (95% CI: 0.37–8.29). In the abdominal aorta, hypercholesterolemic diet resulted in significant downregulation of HOXA5 (95% CI: 0.03–2.74) which was reversed with colchicine/NAC back to baseline (95% CI: −1.19 to 1.51). Colchicine/fenofibrate downregulated HIF1a compared to baseline (95% CI: 0.83–6.44). No significant differences were noted in terms of BMP4, SOX2, and OCT4. Conclusions: Overall, the aortic expression pattern of mechanosensitive genes seems to be spatially influenced by a hyperlipidemic diet and can be modified using colchicine-based therapy.

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Section: Discussionmentioning

confidence: 99%

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens

Mylonas

Sarantis

Kapelouzou

et al. 2022

JCM

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“…After fixing the right carotid artery in 4% paraformaldehyde, embedding it in OCT, and cutting it into frozen sections (6 μm), our team applied HE staining (Wuhan Servicebio Biological Technology Co., Ltd.) to observe carotid plaque area and neointima formation to assess carotid atherosclerotic lesions, stained oil red O working solution (Sigma-Aldrich, St. Louis, U.S.) for 20 min, later decolorized it with 60% isopropanol for 10 min, washed thoroughly in phosphate buffered saline (PBS) and later acquired images under common optical microscopes to evaluate lipid droplet accumulation [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…Our team transferred the protein to PVDF film (Millipore, U.S.), blocking the film in 5% skim milk, via following primary antibodies overnight at 4°C: p-PI3K p85, PI3K p85, p-AKT, AKT, p-mTOR, mTOR, Beclin-1, P62, and GAPDH antibodies (1:1000 dilution). Our team incubated the films with anti-mouse and -rabbit IgG peroxidase-conjugated secondary antibodies, visualized bands with ECL kits (Millipore, U.S.) and quantified them via Quantity One Software (Bio-Rad, U.S.) [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Berberine inhibited carotid atherosclerosis through PI3K/AKTmTOR signaling pathway

Song

Chen

2021

Bioengineered

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Atherosclerosis, a multifactorial vascular disease resulting from lipid metabolism disorders, features chronic inflammatory damage resulting from endothelial dysfunction, which usually affects multiple arteries. The carotid artery is a common site for clinical atherosclerosis evaluation. The aortic root is the standard site for quantifying atherosclerosis in mice. Due to the adverse reactions of first-line drugs, it is necessary to discover new drugs to prevent and treat atherosclerosis. Berberine (BBR) is one of the most promising natural products derived from herbal medicine Coptidis Rhizoma (Huanglian) that features significant anti-atherosclerosis properties. However, overall BBR mechanism against carotid atherosclerosis has not been clearly discovered. Our work aimed to investigate potential BBR mechanism in improving carotid atherosclerosis in ApoE knockout mice. Here, we proved that in ApoE -/mice receiving high-fat diet for 12 weeks, BBR can reduce serum lipid levels, improve intimal hyperplasia, and antagonize carotid lipid accumulation, which may be achieved through regulating the PI3K/AKT/mTOR signaling pathway, regulating autophagy, promoting cell proliferation and inhibiting cell apoptosis. In summary, these data indicate that BBR can ameliorate carotid atherosclerosis. Therefore, it could be a promisingly therapeutic

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“…As previously conveyed by our group, a hyperlipidemic diet induces the expression of the KLF4 gene, which, in turn, dysregulates nitric oxide synthesis, VE-cadherin transcription, intercellular connections, and macrophage/monocyte differentiation [9,[27][28][29][30][31]. Similarly, hindering the overexpression of NANOG, HOXA5, and HIF1α diminishes the proliferative, migratory, and anti-apoptotic capabilities of vascular SMCs [32][33][34][35]. HIF1α downregulation also curtails the production of adhesion molecules such as CXCL1, ICAM-1, and VCAM-1 [36,37].…”

Section: Discussionmentioning

confidence: 79%

Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation

Mylonas,

Peroulis,

Kapelouzou

2023

IJMS

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The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft failures. A total of 42 New Zealand white rabbits were fed hyperlipidemic chow and classified into three groups. A double-stranded Egr-1 ODN was synthesized and infused in vein grafts prior to anastomosis with the common carotid artery. All vein grafts were retrieved at the conclusion of the predefined experimental period. Real-time quantitative polymerase chain reaction was performed to estimate expression patterns for several genes of interest. MYD88, TLR2-4, TLR8, NF-kB, TNF-α, IFNβ, and IFNγ; chemokines CCL4, CCL20, CCR2; numerous interleukins; and stem cell genes KFL4, NANOG, HOXA5, and HIF1α were universally downregulated in the ODN arm compared with the controls. By understanding these multifaceted interactions, our study offers actionable insights that may pave the way for innovative interventions in vascular reconstructions.

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The protective effect of HOXA5 on carotid atherosclerosis occurs by modulating the vascular smooth muscle cell phenotype

Cited by 15 publications

References 44 publications

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens

Berberine inhibited carotid atherosclerosis through PI3K/AKTmTOR signaling pathway

Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation

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