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Adventitial growth factor signalling and vascular remodelling: potential of perivascular gene transfer from the
Richard C M Siow1, Adrian T Churchman
1Cardiovascular Division, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. richard.siow@kcl.ac.uk
Insights
The adventitia, a vessel wall layer, plays a key role in vascular remodeling. Targeting adventitial cells with gene therapy offers a novel approach to treat vascular diseases.
Area of Science:
- Vascular Biology
- Cardiovascular Research
- Cellular and Molecular Medicine
Background:
- The adventitia, traditionally viewed as inert, is increasingly recognized for its role in vascular remodeling.
- Adventitial cells, particularly myofibroblasts, are activated by growth factors like TGF-β1 and PDGF-BB.
- This activation contributes to intimal hyperplasia and vascular diseases such as atherosclerosis and graft failure.
Purpose of the Study:
- To review the evidence for growth factor involvement in adventitial cell function and vascular remodeling.
- To explore the therapeutic potential of targeting the adventitia for vascular disease treatment.
- To highlight 'outside-in' gene transfer strategies for modulating adventitial gene expression.
Main Methods:
- Literature review of studies on adventitial cell biology and vascular remodeling.
- Analysis of research on growth factor signaling pathways (TGF-β1, PDGF-BB) in the adventitia.
- Evaluation of perivascular gene transfer techniques and their therapeutic implications.
Main Results:
- Adventitial myofibroblast activation by growth factors drives vascular remodeling.
- These processes involve progenitor cell recruitment, angiogenesis, and matrix deposition.
- Reactive oxygen species generation is enhanced, contributing to intimal hyperplasia.
- Local growth factors significantly influence vascular function and disease progression.
Conclusions:
- The adventitia is a critical, active player in vascular remodeling and disease.
- Targeting adventitial cells and their signaling pathways holds therapeutic promise.
- Perivascular gene transfer offers a novel 'outside-in' strategy to combat vascular diseases by modulating adventitial activity.
Abstract:
The adventitial segment of the vessel wall has received limited attention compared the endothelium, media and neointima in processes involved in vascular remodelling during atherogenesis, coronary artery bypass graft failure and in response to angioplasty. The adventitia has been regarded as a relatively 'inert' layer providing a supportive connective tissue and extracellular matrix scaffold around vessels for nerves and the vasa vasorum. We and others have recently demonstrated that functional changes in cells within the adventitia contribute to vascular remodelling through the activation and migration of adventitial myofibroblasts, partly under the influence of transforming growth factor-beta1 and platelet derived growth factor-BB. These cytokines stimulate local accumulation of progenitor cells, angiogenesis, matrix deposition and enhanced generation of reactive oxygen species, together contributing to intimal hyperplasia in vascular diseases. This review summarises the evidence that growth factors acting locally in the adventitia can influence vascular function. Furthermore we highlight the therapeutic potential of perivascular gene transfer approaches from the 'outside-in' to antagonise growth factor activity and to modulate expression of vaso- and redox-active genes which act in concert to prevent the progression of vascular diseases in which adventitial cells are activated.
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