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Cellular-scale sex differences in extracellular matrix remodeling by valvular interstitial cells.

LaTonya R Simon1, Ashley J Scott2, Lysmarie Figueroa Rios1

  • 1Department of Biomedical Engineering, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 8531, Madison, WI, 53705, USA.

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|September 7, 2022
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Summary

Sex differences in calcific aortic valve disease (CAVD) involve valvular interstitial cells (VICs). Female VICs show higher collagen production and matrix metalloproteinase (MMP) expression, while male VICs exhibit greater collagenase and gelatinase activity, impacting fibrosis.

Keywords:
Extracellular matrixFibrosisRemodelingSex differences

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Area of Science:

  • Cardiovascular Biology
  • Extracellular Matrix Research
  • Sex Differences in Disease

Background:

  • Calcific aortic valve disease (CAVD) affects males twice as often as females.
  • Female patients with CAVD exhibit greater valve fibrosis than males.
  • Fibrosis involves an imbalance in extracellular matrix (ECM) production and degradation.

Purpose of the Study:

  • To characterize sex-based differences in ECM production and remodeling by valvular interstitial cells (VICs).
  • To understand the contribution of VICs to sexual dimorphism in CAVD fibrosis.

Main Methods:

  • Assessed gene and protein expression of myofibroblastic markers, ECM components, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) in male and female VICs.
  • Measured overall metabolic activity and collagenase/gelatinase activity.
  • Utilized qRT-PCR and western blot techniques.

Main Results:

  • Male VICs produced higher levels of myofibroblastic markers.
  • Female VICs demonstrated greater metabolic activity and collagen production.
  • Females generally showed higher MMP expression, while males had greater collagenase and gelatinase activity. No sex differences in TIMP production were observed.

Conclusions:

  • Significant sex differences exist in VIC-mediated ECM remodeling.
  • These cellular differences may explain the observed sexual dimorphism in CAVD fibrosis and ECM structure.