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Updated: Feb 3, 2026
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
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.
Insights
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.
Aims:
Calcific aortic valve stenosis (CAVS) is characterized by a fibrocalcific process. Studies have shown an association between CAVS and the activation of platelets. It is believed that shear stress associated with CAVS promotes the activation of platelets. However, whether platelets actively participate to the mineralization of the aortic valve (AV) and the progression of CAVS is presently unknown. To identify the role of platelets into the pathobiology of CAVS.
Methods And Results:
Explanted control non-mineralized and mineralized AVs were examined by scanning electron microscope (SEM) for the presence of activated platelets. In-depth functional assays were carried out with isolated human valve interstitial cells (VICs) and platelets as well as in LDLR-/- apoB100/100 IGFII (IGFII) mice. Scanning electron microscope and immunogold markings for glycoprotein IIb/IIIa (GPIIb/IIIa) revealed the presence of platelet aggregates with fibrin in endothelium-denuded areas of CAVS. In isolated VICs, collagen-activated platelets induced an osteogenic programme. Platelet-derived adenosine diphosphate induced the release of autotaxin (ATX) by VICs. The binding of ATX to GPIIb/IIIa of platelets generated lysophosphatidic acid (LysoPA) with pro-osteogenic properties. In IGFII mice with CAVS, platelet aggregates were found at the surface of AVs. Administration of activated platelets to IGFII mice accelerated the development of CAVS by 2.1-fold, whereas a treatment with Ki16425, an antagonist of LysoPA receptors, prevented platelet-induced mineralization of the AV and the progression of CAVS.
Conclusions:
These findings suggest a novel role for platelets in the progression of CAVS.
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