Role of Extracellular Matrix in Cardiovascular Tissue Calcification
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Date
2021-12
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The Ohio State University
Abstract
Biomineralization is a complex process which results in the deposition of calcium phosphate crystals in the form of hydroxyapatite (HA) in mammalian tissues. Calcification of cardiovascular tissue is found in many diseases and leads to many adverse consequences. Collagen fibrils and elastin are major components of the extracellular matrix (ECM) in cardiovascular tissues, yet little is known regarding the calcification of ECM in soft-tissue. The goal of this study was to gain novel insights on how changes in the ECM (caused by matrix receptors) modulate calcification in cardiovascular tissue. Studies were conducted with sections of aortas from wild-type (WT) and DDR1 knockout (KO) mice subjected to biomimetic mineralization protocols. The samples were incubated in modified simulated body fluid (mSBF) or polymer-induced liquid-precursor (PILP) to mediate extra or intra-fibrillar mineralization, respectively. Following the incubations, all samples were embedded and frozen in optimal cutting temperature media, sectioned and Von Kossa stained to evaluate the presence of calcific deposits. In addition to the Von Kossa staining, an analysis of trichrome stains on WT and DDR1 KO mice was conducted to further understand potential mechanisms behind calcification in cardiovascular tissue. Results from both the PILP and mSBF groups indicate that absence of DDR1 results in attenuation of vascular calcification on elastin in murine aortas. These findings indicate that changes in the ECM can be a driver of vascular calcification, independent of cell-mediated processes.
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Keywords
Extracellular Matrix, Discoidin Domain Receptors, Cardiovascular Mineralization, Biomimetic Mineralization