TY - JOUR
T1 - Extracellular vesicles
T2 - the key to unlocking mechanisms of age-related vascular disease?
AU - Whitehead, Meredith
AU - Antonazzi, Marco
AU - Shanahan, Catherine M.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/4
Y1 - 2024/4
N2 - Aging is associated with the development of two ubiquitous, detrimental pathologies, vascular calcification and amyloidosis. These pathologies are characterized by the accumulation of toxic aggregates in the vessel extracellular matrix (ECM) in the form of crystalline calcium and phosphate mineral or insoluble protein fibrils, respectively. These aggregates impact ECM integrity, drive vascular stiffening, and can also cause cell death and phenotypic change in the cells that interact with them. The deposition of both calcification and amyloid requires a nucleus that can mediate the mineralization of calcium and phosphate, or amyloid aggregation from precursor proteins or peptides. Emerging evidence suggests that changes in the composition of the ECM associated with cellular senescence, as well as extracellular vesicle (EV) release, cargo-loading, trapping, and aggregation within the ECM, are common and synergistic mechanisms that regulate the development of these pathologies. Importantly, vascular smooth muscle cells (VSMCs) orchestrate the formation of both pathologies that commonly co-occur in the aging vasculature. Here, we outline the commonalities and differences in what is known about the genesis of calcification and amyloid, and highlight key questions and areas that remain unknown and require further investigation. The complex relationship between senescence, EVs, and the ECM, mediated by VSMCs, which drives the accumulation of HA and amyloid, could be a target for therapeutic intervention.
AB - Aging is associated with the development of two ubiquitous, detrimental pathologies, vascular calcification and amyloidosis. These pathologies are characterized by the accumulation of toxic aggregates in the vessel extracellular matrix (ECM) in the form of crystalline calcium and phosphate mineral or insoluble protein fibrils, respectively. These aggregates impact ECM integrity, drive vascular stiffening, and can also cause cell death and phenotypic change in the cells that interact with them. The deposition of both calcification and amyloid requires a nucleus that can mediate the mineralization of calcium and phosphate, or amyloid aggregation from precursor proteins or peptides. Emerging evidence suggests that changes in the composition of the ECM associated with cellular senescence, as well as extracellular vesicle (EV) release, cargo-loading, trapping, and aggregation within the ECM, are common and synergistic mechanisms that regulate the development of these pathologies. Importantly, vascular smooth muscle cells (VSMCs) orchestrate the formation of both pathologies that commonly co-occur in the aging vasculature. Here, we outline the commonalities and differences in what is known about the genesis of calcification and amyloid, and highlight key questions and areas that remain unknown and require further investigation. The complex relationship between senescence, EVs, and the ECM, mediated by VSMCs, which drives the accumulation of HA and amyloid, could be a target for therapeutic intervention.
KW - amyloid
KW - calcification
KW - extracellular vesicles
KW - Senescence
KW - vascular smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=85184699183&partnerID=8YFLogxK
U2 - 10.20517/jca.2023.49
DO - 10.20517/jca.2023.49
M3 - Review article
AN - SCOPUS:85184699183
SN - 2768-5993
VL - 4
JO - Journal of Cardiovascular Aging
JF - Journal of Cardiovascular Aging
IS - 2
M1 - 12
ER -