Title:Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling
Volume: 11
Issue: 5
Author(s): Jinjutha Silpanisong and William J. Pearce
Affiliation:
Keywords:
Cerebrovascular circulation, chronic hypoxia, fetal maturation, growth factors, receptor tyrosine kinases, smooth
muscle phenotype.
Abstract: Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors
to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling
can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling.
Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and
its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia
can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein
coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor
(HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of
HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine
kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and
angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent
factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate
in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different
responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic
demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and
heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation.
