The Extracellular Matrix in the Age-Related Impairment of Angiogenesis
The density of capillary networks declines with aging, the result of a progressive impairment of the complex process of angiogenesis responsible for growing new vessels. This loss of the smallest components of the circulatory system is likely important in the progression of aging, in that it affects blood pressure and deprives energy-hungry tissues such as muscle and brain of the oxygen and nutrients needed for correct function.
Researchers here view this aspect of vascular aging through the lens of the extracellular matrix, a tissue feature that also changes with age in ways known to be detrimental. Are these changes an important contributing cause of impaired angiogenesis? For any manifestation of aging, it is a challenge to determine which of the potential contributing causes are more or less important, given the inability to intervene in a very selective, pinpoint way. It is most likely faster and better to try to fix every potential issue, finding out along the way that some are not in fact all that important, than to first try to understand which processes should be targeted.
Angiogenesis is the process by which new capillaries form by sprouting from pre-existing ones. Each step in angiogenesis is regulated by the extracellular matrix (ECM). This process involves the migration, proliferation, and differentiation of endothelial cells (ECs) and pericytes and results in elongation of the initial tip, followed by anastomosis with other blood vessels to form perfused vascular branches. Accumulating evidence indicates that angiogenesis is impaired in older adults, contributing to cardiovascular and cerebrovascular disease and delayed wound healing, reducing the quality of life and causing a significant burden for healthcare systems.
Evidence indicates that ageing-related changes in the ECM driven by cellular senescence lead to a reduction in neovascularisation, reduced microvascular density, and an increased risk of tissue ischaemic injury. Elucidating interactions between the ECM and cells during angiogenesis in the context of ageing is necessary to clarify the mechanisms underlying reduced angiogenesis in older adults. In this review, we summarize ageing-related changes in the composition, structure, and function of the ECM and their relevance for angiogenesis. Then, we explore in detail the mechanisms of interaction between the aged ECM and cells during impaired angiogenesis in the older population for the first time, discussing diseases caused by restricted angiogenesis.
We also outline several novel pro-angiogenic therapeutic strategies targeting the ECM that can provide new insights into the choice of appropriate treatments for a variety of age-related diseases. Based on the knowledge gathered from recent reports and journal articles, we provide a better understanding of the mechanisms underlying impaired angiogenesis with age and contribute to the development of effective treatments that will enhance quality of life.