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Measuring the Stiffness of Ex Vivo Mouse Aortas Using Atomic Force Microscopy
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Measuring the Stiffness of Ex Vivo Mouse Aortas Using Atomic Force Microscopy

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Increased vascular smooth muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension

Nancy L Sehgel1, Yi Zhu, Zhe Sun

  • 1Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey;

American Journal of Physiology. Heart and Circulatory Physiology
|May 28, 2013
PubMed

Insights

Hypertension increases vascular stiffness due to changes in vascular smooth muscle cells, not just the extracellular matrix. This finding offers new therapeutic targets for hypertension and vascular stiffness.

Area of Science:

  • Cardiovascular Science
  • Biomedical Engineering
  • Cellular Mechanics

Background:

  • Vascular stiffness is a key factor in hypertension and its complications like atherosclerosis.
  • Current understanding attributes vascular stiffness primarily to extracellular matrix and endothelial factors.
  • The role of intrinsic vascular smooth muscle cell (VSMC) mechanical properties remains under-explored.

Purpose of the Study:

  • To investigate the hypothesis that increased large-artery stiffness in hypertension involves intrinsic VSMC mechanical properties.
  • To explore the dynamic component of cellular elastic stiffness in hypertension.
  • To identify potential therapeutic targets within VSMCs for managing hypertension-related vascular stiffness.

Main Methods:

  • Utilized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive controls.
  • Employed an engineered aortic tissue model to assess VSMC stiffness.
  • Applied atomic force microscopy (AFM) nanoindentation for precise measurement of cellular elastic stiffness.
  • Investigated the effect of VSMC cytoskeletal protein inhibitors on cellular stiffness.

Main Results:

  • Confirmed increased aortic stiffness and arterial pressure in SHR compared to WKY rats.
  • Demonstrated significantly increased elastic stiffness in aortic VSMCs from SHR versus WKY rats.
  • Observed altered temporal oscillations in VSMC stiffness in hypertensive rats, indicating a dynamic change.
  • Showed that inhibitors of VSMC cytoskeletal proteins effectively reduced cellular stiffness in both hypertensive and control groups.

Conclusions:

  • This study provides the first evidence that individual VSMC stiffness contributes to overall vascular stiffness in hypertension.
  • Altered intrinsic mechanical properties of VSMCs represent a novel mechanism underlying hypertension-induced vascular stiffness.
  • These findings suggest that targeting VSMC stiffness may offer new therapeutic strategies for hypertension and associated vascular complications.

Keywords:
atomic force microscopyhypertensionpulse wave velocityvascular smooth musclevascular stiffness

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