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Abstract The cardiovascular system functions under continuous cyclic mechanical stretch, with disruptions in mechanical and biochemical signals contributing to disease progression. In cardiovascular disorders, these disruptions activate cardiac fibroblasts (CFs) and promote cellular senescence, yet it remains unclear whether mechanical stimuli alone can initiate this phenotype. Here, primary murine CFs are exposed to uniaxial stretch, and systematically varied mechanical parameters assessed their role in senescence induction. Loss of stretch magnitude and increase in frequency, mimicking a pathologic hypertrophy and fibrosis, led to a senescence phenotype, identified through cell cycle arrest, decreased lamin B expression, and DNA damage. Mechanically‐induced CF senescence depends on p53/p21, whereas senescence triggered by oxidative stress or lamin A/C mutation proceeded via p16. Notably, mechanically‐induced premature senescence is accompanied by reduced levels of the nuclear envelope protein emerin. These findings demonstrate that altered mechanical signals are sufficient to trigger premature senescence and implicate compromised nuclear integrity in the underlying mechanism.more » « less
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Intervertebral disc (IVD) degeneration is a significant health issue that can lead to severe complications. Recent research has highlighted the close relationship between disc degeneration and the biomechanical properties of the IVD. This study introduces an innovative approach—magnetic resonance imaging (MRI) elastography of the human IVD—using an explicit inverse solver to identify the non-homogeneous shear modulus map of the IVD. The key advantage of this explicit solver is its streamlined optimization process, focusing only on the shear moduli of the nucleus pulposus (NP), annulus fibrosus (AF), and their interface. This approach reduces the optimization variables, making it more efficient than traditional pixel-based approaches. To validate this method, we conducted a plane strain numerical example, observing a consistent underestimation of the AF/NP shear modulus ratio by a scaling factor of approximately 1.5. Further investigations included comprehensive sensitivity analyses to various noise levels, revealing that the proposed method accurately characterizes shear modulus distribution in the AF and NP regions, with a maximum relative error of the AF/NP shear modulus ratio remaining below 8%. In addition, applying this approach to real human IVDs underin vitrocompression or bending, demonstrated its effectiveness, yielding an AF/NP shear modulus ratio within a reasonable range of 6–15. In summary, the proposed method offers a promising direction for MRI elastography of the human IVD.more » « lessFree, publicly-accessible full text available June 1, 2026
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