Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers
Annually, peripheral arterial disease is estimated to cost over USD 21 billion and diabetic foot disease an estimated at USD 9–13 billion. Mirabegron is a TGA-approved beta-3 adrenoreceptor agonist, shown to be safe and effective in the treatment of overactive bladder syndrome by stimulating bladder...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/12/3187 |
| _version_ | 1797381945196281856 |
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| author | Cameron J. F. Evans Sarah J. Glastras Owen Tang Gemma A. Figtree |
| author_facet | Cameron J. F. Evans Sarah J. Glastras Owen Tang Gemma A. Figtree |
| author_sort | Cameron J. F. Evans |
| collection | DOAJ |
| description | Annually, peripheral arterial disease is estimated to cost over USD 21 billion and diabetic foot disease an estimated at USD 9–13 billion. Mirabegron is a TGA-approved beta-3 adrenoreceptor agonist, shown to be safe and effective in the treatment of overactive bladder syndrome by stimulating bladder smooth muscle relaxation. In this review, we discuss the potential use of beta-3 adrenoreceptor agonists as therapeutic agents repurposed for peripheral arterial disease and diabetic foot ulcers. The development of both conditions is underpinned by the upregulation of oxidative stress pathways and consequential inflammation and hypoxia. In oxidative stress, there is an imbalance of reactive oxygen species and nitric oxide. Endothelial nitric oxide synthase becomes uncoupled in disease states, producing superoxide and worsening oxidative stress. Agonist stimulation of the beta-3 adrenoreceptor recouples and activates endothelial nitric oxide synthase, increasing the production of nitric oxide. This reduces circulating reactive oxygen species, thus decreasing redox modification and dysregulation of cellular proteins, causing downstream smooth muscle relaxation, improved endothelial function and increased angiogenesis. These mechanisms lead to endothelial repair in peripheral arterial disease and an enhanced perfusion in hypoxic tissue, which will likely improve the healing of chronic ulcers. |
| first_indexed | 2024-03-08T20:58:22Z |
| format | Article |
| id | doaj.art-16e3bc02cadc40e8b191b9e3c5960bcf |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T20:58:22Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-16e3bc02cadc40e8b191b9e3c5960bcf2023-12-22T13:54:54ZengMDPI AGBiomedicines2227-90592023-11-011112318710.3390/biomedicines11123187Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot UlcersCameron J. F. Evans0Sarah J. Glastras1Owen Tang2Gemma A. Figtree3Kolling Institute, University of Sydney, Sydney, NSW 2006, AustraliaKolling Institute, University of Sydney, Sydney, NSW 2006, AustraliaKolling Institute, University of Sydney, Sydney, NSW 2006, AustraliaKolling Institute, University of Sydney, Sydney, NSW 2006, AustraliaAnnually, peripheral arterial disease is estimated to cost over USD 21 billion and diabetic foot disease an estimated at USD 9–13 billion. Mirabegron is a TGA-approved beta-3 adrenoreceptor agonist, shown to be safe and effective in the treatment of overactive bladder syndrome by stimulating bladder smooth muscle relaxation. In this review, we discuss the potential use of beta-3 adrenoreceptor agonists as therapeutic agents repurposed for peripheral arterial disease and diabetic foot ulcers. The development of both conditions is underpinned by the upregulation of oxidative stress pathways and consequential inflammation and hypoxia. In oxidative stress, there is an imbalance of reactive oxygen species and nitric oxide. Endothelial nitric oxide synthase becomes uncoupled in disease states, producing superoxide and worsening oxidative stress. Agonist stimulation of the beta-3 adrenoreceptor recouples and activates endothelial nitric oxide synthase, increasing the production of nitric oxide. This reduces circulating reactive oxygen species, thus decreasing redox modification and dysregulation of cellular proteins, causing downstream smooth muscle relaxation, improved endothelial function and increased angiogenesis. These mechanisms lead to endothelial repair in peripheral arterial disease and an enhanced perfusion in hypoxic tissue, which will likely improve the healing of chronic ulcers.https://www.mdpi.com/2227-9059/11/12/3187diabetes mellitusperipheral arterial diseasewoundulcersoxidative stressangiogenesis |
| spellingShingle | Cameron J. F. Evans Sarah J. Glastras Owen Tang Gemma A. Figtree Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers Biomedicines diabetes mellitus peripheral arterial disease wound ulcers oxidative stress angiogenesis |
| title | Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers |
| title_full | Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers |
| title_fullStr | Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers |
| title_full_unstemmed | Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers |
| title_short | Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers |
| title_sort | therapeutic potential for beta 3 adrenoreceptor agonists in peripheral arterial disease and diabetic foot ulcers |
| topic | diabetes mellitus peripheral arterial disease wound ulcers oxidative stress angiogenesis |
| url | https://www.mdpi.com/2227-9059/11/12/3187 |
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