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FUNCTIONAL COUPLING OF VALVULAR INTERSTITIAL CELLS AND COLLAGEN VIA α2β1 INTEGRINS IN THE MITRAL LEAFLET
Elizabeth H Stephens1, Christopher A Durst1, Julia C Swanson2
1Department of Bioengineering, Rice University, Houston, TX.
Cellular and Molecular Bioengineering
|October 13, 2023
Summary
Valvular interstitial cells (VICs) actively generate force in the mitral valve. Actin-mediated VIC force generation, coupled to collagen via alpha2beta1 integrins, is essential for mitral leaflet function.
Area of Science:
- Cardiovascular Biology
- Biomedical Engineering
- Cellular Mechanics
Background:
- Mitral leaflets were previously considered passive structures.
- Mitral leaflets are now recognized as dynamic, active tissues.
- Valvular interstitial cells (VICs) are contractile and may generate force.
Purpose of the Study:
- To investigate the mechanisms of VICs in mitral leaflet force generation.
- To test if actin-mediated VIC force generation coupled to collagen via alpha2beta1 integrins is necessary for mitral leaflet force generation.
Main Methods:
- High magnification fluorescent imaging of porcine mitral leaflets.
- Functional studies of isometric force development.
- Pharmacological inhibition of alpha2beta1 integrins and actin polymerization.
Main Results:
- VIC cytoplasm was observed to conform tightly to collagen fibers.
- Actin within VICs appeared to attach to collagen fibers.
- Blocking alpha2beta1 integrins or actin polymerization abolished KCl-induced force development.
Conclusions:
- VIC-collagen coupling, mediated by alpha2beta1 integrins, is crucial for mitral leaflet force generation.
- This mechanism may play a significant role in in vivo mitral valve function.
Keywords:
actincell contractionconfocal microscopycytochalasinextracellular matrixforce generationheart valveintegrinsecond harmonic generationMore Related Videos
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