Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor
Abstract
This review elucidates the roles of capillary haemodynamics, nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the remodelling of skeletal muscle microcirculation in response to increased (electrical stimulation) or decreased (chronic ischaemia) blood flow. During early stages of stimulation-induced angiogenesis, up-regulation of VEGF and its receptor VEGF receptor 2 is dependent on shear stress and NO release, whereas later, involvement of NO in the expanding capillary bed appears to be VEGF/VEGF receptor 2 independent. Arteriolar growth most likely relies on mechanical wall stresses while growth factor involvement is less clear. By contrast, in muscles with restricted blood flow, increased VEGF/VEGF receptor 2 expression after ischaemia onset is not associated with changes in shear stress or hypoxia, or capillary growth. After several weeks, VEGF protein levels are lower than normal while modest angiogenesis takes place, a temporal mismatch that limits the utility of using growth factor levels during ischaemia to assess angiogenic potential. Chronic stimulation of ischaemic muscles restores their depressed endothelial-dependent arteriolar dilatation, increases capillary shear stress and VEGF receptor 2 and promotes capillary growth. In patients with peripheral vascular disease, electrical stimulation of ischaemic calf muscles increases blood flow, capillary surface area and muscle performance, offering an alternative 'endogenous' treatment to gene or cell therapy.
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NO bioavailability plays an important role modulating chronic tissue ischemia responses.
“NO bioavailability also plays an important role modulating chronic tissue ischemia responses [168, 169].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [168]
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- Authors
- Hudlicka, O., & Brown, M. D.
- Affiliations
- University of Birmingham (GB)
- Venue
- Journal of Vascular Research
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 46
- Issue
- 5
- Pages
- 504-512
- ISSN
- 1018-1172 (ISSN-L)
- 1423-0135
- OpenAlex
- W2058170745
- Cited by
- 150
- References
- 73
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 16 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 10 · 2014: 10 · 2013: 6 · 2012: 11
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Vascular Research (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- skeletal muscle microcirculation, shear stress, nitric oxide, vascular endothelial growth factor, VEGF receptor 2, angiogenesis, electrical stimulation, arteriolar dilatation, peripheral vascular disease, muscle blood flow
- MeSH terms
- Adaptation, Physiological, Animals, Electric Stimulation, Humans, Ischemia, Microcirculation, Nitric Oxide, Regional Blood Flow, Stress, Mechanical, Muscle, Skeletal, Vascular Endothelial Growth Factor A
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