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05:47
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
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Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis
Rihab Bouchareb1, Marie-Chloé Boulanger1, Lionel Tastet2
1Laboratory of Cardiovascular Pathobiology, Department of Surgery, Quebec Heart and Lung Institute/Research Center, Laval University, 2725 chemin Ste-Foy, Quebec, Canada.
European Heart Journal
|November 6, 2018
Summary
Platelets actively contribute to calcific aortic valve stenosis (CAVS) progression by promoting aortic valve mineralization. Inhibiting platelet-derived lysophosphatidic acid signaling significantly reduces CAVS development.
Area of Science:
- Cardiovascular Biology
- Hematology
- Biomaterials Science
Background:
- Calcific aortic valve stenosis (CAVS) involves a fibrocalcific process.
- Platelet activation is associated with CAVS, potentially due to shear stress.
- The specific role of platelets in aortic valve mineralization and CAVS progression remains unclear.
Purpose of the Study:
- To elucidate the role of platelets in the pathobiology of CAVS.
- To investigate platelet participation in aortic valve mineralization.
Main Methods:
- Scanning electron microscopy (SEM) and immunogold labeling of explanted aortic valves (AVs).
- Functional assays using isolated human valve interstitial cells (VICs) and platelets.
- In vivo studies in LDLR-/- apoB100/100 IGFII (IGFII) mice with induced CAVS.
Main Results:
- Platelet aggregates and fibrin were observed in CAVS AVs.
- Activated platelets induced an osteogenic program in VICs.
- Platelet-derived adenosine diphosphate (ADP) stimulated VICs to release autotaxin (ATX), which generated pro-osteogenic lysophosphatidic acid (LysoPA) via GPIIb/IIIa.
- Platelet administration accelerated CAVS in mice; LysoPA receptor antagonism prevented mineralization and progression.
Conclusions:
- Platelets play a significant, previously unrecognized role in CAVS progression.
- Platelet activation and subsequent LysoPA generation are key drivers of aortic valve mineralization.
- Targeting platelet-derived LysoPA signaling represents a potential therapeutic strategy for CAVS.
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