[HTML][HTML] Age-related vascular stiffening: causes and consequences

JC Kohn, MC Lampi, CA Reinhart-King - Frontiers in genetics, 2015 - frontiersin.org
Frontiers in genetics, 2015frontiersin.org
Arterial stiffening occurs with age and is closely associated with the progression of
cardiovascular disease. Stiffening is most often studied at the level of the whole vessel
because increased stiffness of the large arteries can impose increased strain on the heart
leading to heart failure. Interestingly, however, recent evidence suggests that the impact of
increased vessel stiffening extends beyond the tissue scale and can also have deleterious
microscale effects on cellular function. Altered extracellular matrix (ECM) architecture has …
Arterial stiffening occurs with age and is closely associated with the progression of cardiovascular disease. Stiffening is most often studied at the level of the whole vessel because increased stiffness of the large arteries can impose increased strain on the heart leading to heart failure. Interestingly, however, recent evidence suggests that the impact of increased vessel stiffening extends beyond the tissue scale and can also have deleterious microscale effects on cellular function. Altered extracellular matrix (ECM) architecture has been recognized as a key component of the pre-atherogenic state. Here, the underlying causes of age-related vessel stiffening are discussed, focusing on age-related crosslinking of the ECM proteins as well as through increased matrix deposition. Methods to measure vessel stiffening at both the macro- and microscale are described, spanning from the pulse wave velocity measurements performed clinically to microscale measurements performed largely in research laboratories. Additionally, recent work investigating how arterial stiffness and the changes in the ECM associated with stiffening contributed to endothelial dysfunction will be reviewed. We will highlight how changes in ECM protein composition contribute to atherosclerosis in the vessel wall. Lastly, we will discuss very recent work that demonstrates endothelial cells (ECs) are mechano-sensitive to arterial stiffening, where changes in stiffness can directly impact EC health. Overall, recent studies suggest that stiffening is an important clinical target not only because of potential deleterious effects on the heart but also because it promotes cellular level dysfunction in the vessel wall, contributing to a pathological atherosclerotic state.
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