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Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens
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 atheroprotect...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656280/ https://www.ncbi.nlm.nih.gov/pubmed/36362692 http://dx.doi.org/10.3390/jcm11216465 |
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author | Mylonas, Konstantinos S. Sarantis, Panagiotis Kapelouzou, Alkistis Karamouzis, Michalis V. Kapetanakis, Emmanouil I. Kontzoglou, Konstantinos Iliopoulos, Dimitrios C. Nikiteas, Nikolaos Schizas, Dimitrios |
author_facet | Mylonas, Konstantinos S. Sarantis, Panagiotis Kapelouzou, Alkistis Karamouzis, Michalis V. Kapetanakis, Emmanouil I. Kontzoglou, Konstantinos Iliopoulos, Dimitrios C. Nikiteas, Nikolaos Schizas, Dimitrios |
author_sort | Mylonas, Konstantinos S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9656280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96562802022-11-15 Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens Mylonas, Konstantinos S. Sarantis, Panagiotis Kapelouzou, Alkistis Karamouzis, Michalis V. Kapetanakis, Emmanouil I. Kontzoglou, Konstantinos Iliopoulos, Dimitrios C. Nikiteas, Nikolaos Schizas, Dimitrios J Clin Med Article 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. MDPI 2022-10-31 /pmc/articles/PMC9656280/ /pubmed/36362692 http://dx.doi.org/10.3390/jcm11216465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mylonas, Konstantinos S. Sarantis, Panagiotis Kapelouzou, Alkistis Karamouzis, Michalis V. Kapetanakis, Emmanouil I. Kontzoglou, Konstantinos Iliopoulos, Dimitrios C. Nikiteas, Nikolaos Schizas, Dimitrios Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title | Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title_full | Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title_fullStr | Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title_full_unstemmed | Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title_short | Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens |
title_sort | mechanosensitive stem-cell genes and klotho in atherosclerotic aortas: regulating spatially deranged expression patterns using colchicine regimens |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656280/ https://www.ncbi.nlm.nih.gov/pubmed/36362692 http://dx.doi.org/10.3390/jcm11216465 |
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