Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries
The normal ageing process affects resistance arteries, leading to various functional and structural changes. Systolic hypertension is a common occurrence in human ageing, and it is associated with large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microv...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2601 |
| _version_ | 1797264415489261568 |
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| author | Lars Jørn Jensen |
| author_facet | Lars Jørn Jensen |
| author_sort | Lars Jørn Jensen |
| collection | DOAJ |
| description | The normal ageing process affects resistance arteries, leading to various functional and structural changes. Systolic hypertension is a common occurrence in human ageing, and it is associated with large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, a progressive elevation in the mean arterial pressure is evidenced by clinical and epidemiological data as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. The dysregulation of calcium entry channels (L-type, T-type, and TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to the age-related dysregulation of myogenic tone. Flow-mediated vasodilation, a hallmark of endothelial function, is compromised in ageing. This endothelial dysfunction is related to increased oxidative stress, lower nitric oxide bioavailability, and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall that is typically observed in conjunction with outward remodeling (in normotension), or as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of actin cytoskeletal components, and extracellular matrix fiber proteins. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation play substantial roles in age-related vascular dysfunction. Due to its role in the regulation of vascular tone and structural proteins, the RhoA/Rho-kinase pathway is an important target in age-related vascular dysfunction and diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance the overall vascular health. |
| first_indexed | 2024-04-25T00:28:32Z |
| format | Article |
| id | doaj.art-18395c49eb974567834f866d71a2a34f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:28:32Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-18395c49eb974567834f866d71a2a34f2024-03-12T16:45:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255260110.3390/ijms25052601Functional, Structural and Proteomic Effects of Ageing in Resistance ArteriesLars Jørn Jensen0Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg C, DenmarkThe normal ageing process affects resistance arteries, leading to various functional and structural changes. Systolic hypertension is a common occurrence in human ageing, and it is associated with large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, a progressive elevation in the mean arterial pressure is evidenced by clinical and epidemiological data as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. The dysregulation of calcium entry channels (L-type, T-type, and TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to the age-related dysregulation of myogenic tone. Flow-mediated vasodilation, a hallmark of endothelial function, is compromised in ageing. This endothelial dysfunction is related to increased oxidative stress, lower nitric oxide bioavailability, and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall that is typically observed in conjunction with outward remodeling (in normotension), or as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of actin cytoskeletal components, and extracellular matrix fiber proteins. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation play substantial roles in age-related vascular dysfunction. Due to its role in the regulation of vascular tone and structural proteins, the RhoA/Rho-kinase pathway is an important target in age-related vascular dysfunction and diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance the overall vascular health.https://www.mdpi.com/1422-0067/25/5/2601ageingresistance arterymyogenic toneflow-mediated vasodilationstructural remodelinghypertension |
| spellingShingle | Lars Jørn Jensen Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries International Journal of Molecular Sciences ageing resistance artery myogenic tone flow-mediated vasodilation structural remodeling hypertension |
| title | Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries |
| title_full | Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries |
| title_fullStr | Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries |
| title_full_unstemmed | Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries |
| title_short | Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries |
| title_sort | functional structural and proteomic effects of ageing in resistance arteries |
| topic | ageing resistance artery myogenic tone flow-mediated vasodilation structural remodeling hypertension |
| url | https://www.mdpi.com/1422-0067/25/5/2601 |
| work_keys_str_mv | AT larsjørnjensen functionalstructuralandproteomiceffectsofageinginresistancearteries |