An international consortium led by Nature reviews molecular and biomechanical drivers of arterial stiffness, integrating evidence on endothelial dysfunction, VSMC changes, and ECM remodeling to inform novel cardiovascular aging interventions.
Key points
Elevated PWV quantifies arterial elasticity loss and predicts cardiovascular risk.
ECM degradation and collagen crosslinking reshape vessel structure, driving stiffness.
VSMC phenotype switching and inflammatory signaling pathways amplify arterial aging.
Why it matters:
Mapping molecular and biomechanical drivers of arterial stiffening offers pathways to novel cardiovascular anti-aging treatments.
Q&A
What is pulse wave velocity (PWV)?
How does extracellular matrix remodeling contribute to stiffness?
What triggers vascular smooth muscle cell (VSMC) phenotype switching?
Why is endothelial dysfunction critical in vascular aging?
Can arterial stiffness be reversed?
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Academy
Pulse Wave Velocity and Vascular Aging
Pulse Wave Velocity (PWV) is a measure of how fast blood pressure waves move through the arteries. Healthy, elastic arteries transmit these waves more slowly, while stiffer arteries transmit them faster. Over time, repeated cardiac contractions subject large arteries—particularly the aorta—to cyclic mechanical stress, causing gradual elastin fatigue and fragmentation. As elastin breaks down and collagen fibers accumulate, the vessel wall becomes less compliant. Higher PWV readings therefore serve as an accessible, non‐invasive biomarker of vascular aging, reflecting underlying changes in the vessel wall structure and function that contribute to cardiovascular risk.
Extracellular Matrix Remodeling
The extracellular matrix (ECM) in arterial walls is composed mainly of two structural proteins: elastin and collagen. Elastin provides resilience and elastic recoil, while collagen offers tensile strength and structural support. Throughout life, matrix metalloproteinases (MMPs) and other proteases regulate ECM turnover, ensuring balanced remodeling. However, chronic low‐grade inflammation, oxidative stress, and age‐related dysregulation lead to excessive elastin degradation and increased collagen crosslinking. Enzymatic fragmentation of elastin reduces energy storage capacity, while stiff collagen bundles accrue and resist stretch. This shift in the elastin–collagen ratio fundamentally alters the mechanical properties of arteries, raising stiffness and pulse pressure.
Vascular Smooth Muscle Cell Phenotype Switching
Vascular smooth muscle cells (VSMCs) normally reside in a quiescent, contractile state, modulating vascular tone in response to physiological cues. Under pathological stimuli—such as inflammatory cytokines (e.g., TNF-α), growth factors (e.g., PDGF, TGF-β), or biomechanical stress—VSMCs transition to a synthetic phenotype. In this phenotype, they proliferate, migrate, and secrete ECM components and matrix‐modifying enzymes. They may also adopt macrophage-like properties, contributing to local inflammation. Phenotype switching amplifies ECM remodeling and stiffens vascular walls. Understanding the signals that govern VSMC plasticity offers therapeutic avenues to preserve vessel compliance and combat age-related vascular dysfunction.
