ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Heart Valve Disease
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1655341
This article is part of the Research TopicBiomechanics and Mechanotransduction in Cardiovascular CalcificationView all 5 articles
Oxidative low-density lipoprotein and shear induced calcification within a calcific aortic valve disease-on-a-chip platform
Provisionally accepted
- Binghamton University, Binghamton, United States
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Early-stage calcific aortic valve disease (CAVD) has been characterized by the infiltration of immune cells, reorganization of the extracellular matrix, and the deposition and oxidation of low-density lipoproteins (oxLDL). Worldwide studies have revealed that aortic valve disease accounts for up to 43% of patients exhibiting heart disease. Given that there is no targeted therapeutic for CAVD, researchers are investigating disease mechanisms in both onset and progression to develop new drug interventions. We utilized a CAVD-on-a-chip platform of the aortic valve fibrosa to assess the hypothesis that culture calcification will increase with endothelial cell presence, increased oxLDL concentration (25 μg/mL or 50 μg/mL), and shear stress (20 dyne/cm2). CAVD chips consisted of collagen I hydrogel with porcine aortic valve interstitial cells embedded and porcine aortic valve endothelial cells seeded on top of the matrix for up to two days. Here, we demonstrate that the presence of endothelial cells and shear stress drives alkaline phosphatase activity, sulfated glycosaminoglycan production, and the formation of mono-, di-, and octa-calcium phosphates, and hydroxyapatites. Two-day dynamic cultures showed 3D cell-oxLDL interactions, leading to extracellular matrix remodeling and endothelial dysfunction. Given that CAVD has no targeted intervention, continued evolution of this model can lead to significant contributions in preclinical drug development.
Keywords: lipoprotein1, shear stress2, aortic valve3, calcification4, microfluidics5, microphysiological system6
Received: 27 Jun 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Mendoza, Chen, Huang and Mahler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gretchen J. Mahler, gmahler@binghamton.edu
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