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Updated: May 13, 2026

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
05:47

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro

Published on: May 10, 2021

Side-specific endothelial-dependent regulation of aortic valve calcification: interplay of hemodynamics and nitric

Jennifer Richards1, Ismail El-Hamamsy, Si Chen

  • 1Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.

The American Journal of Pathology
|March 19, 2013
PubMed

Insights

Aortic valve endothelial cells (VEC) release nitric oxide (NO), inhibiting valve interstitial cell (VIC) calcification. This NO pathway is crucial for maintaining aortic valve health and preventing early calcification.

Area of Science:

  • Cardiovascular Biology
  • Vascular Physiology
  • Biomaterials Science

Background:

  • Arterial endothelial cells are vital for vascular homeostasis and vessel tone via nitric oxide (NO) secretion.
  • Aortic valve interstitial cells (VICs) are key players in valve structure, and their calcification contributes to pathology.
  • Understanding the interplay between valve endothelial cells (VECs) and VICs is crucial for addressing aortic valve disease.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) produced by aortic valve endothelial cells (VECs) in regulating aortic valve interstitial cell (VIC) phenotype and matrix calcification.
  • To elucidate the mechanisms by which VEC-derived NO influences VIC osteogenic differentiation and calcification.
  • To determine the impact of mechanical stress and NO signaling on aortic valve calcification.

Main Methods:

  • Utilized an in vitro collagen hydrogel culture system to study three-dimensionally cultured porcine VICs and VECs.
  • Employed NO donors (DETA-NO) and blockers (l-NAME) to assess NO's effect on VIC calcification and differentiation.
  • Analyzed endothelial NO synthase (eNOS) expression in porcine and human aortic valves under various conditions.
  • Investigated the role of soluble guanylyl cyclase (sGC) inhibition (ODQ) and shear stress on valve cells.

Main Results:

  • Porcine VICs calcify in osteogenic medium primarily under mechanical stress, and co-culture with VECs significantly attenuates this calcification.
  • VEC-derived NO inhibits VIC myofibroblastic activation, osteogenic differentiation, and calcium deposition.
  • Endothelial NO synthase (eNOS) is expressed in VECs but not VICs, and its expression decreases in osteogenic conditions and in calcified human valves.
  • NO signaling pathways, including cGMP production stimulated by shear stress, are critical in preventing early valve calcification.

Conclusions:

  • Valve endothelial-derived NO acts as a natural inhibitor of early-stage aortic valve calcification.
  • NO signaling is an important regulator of aortic valve homeostasis and plays a protective role against pathological calcification.
  • Targeting the VEC-NO pathway may offer therapeutic strategies for preventing or treating aortic valve calcification.

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