Characterization of Changes in Extracellular Matrix and Cellular Phenotypes in Early Calcific Aortic Valve Disease

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OCLC: 1033020028

Abstract

Calcific aortic valve disease (CAVD) is a prevalent disease associated with severe clinical outcomes and without an effective medical treatment. While advanced disease is well- characterized, there is an unmet scientific need to understand the active pathobiological processes that promote eventual calcification and stenosis of the valve. Using a porcine model of early CAVD, histological staining was used to identify the changes that occur in the extracellular matrix (ECM) with a focus on proteoglycan content. Putatively more advanced lesions were morphologically dense with increased biglycan, decreased hyaluronan, and higher ApoB score and Sox9 fraction. These microenvironmental changes were used to delineate populations of valve interstitial cells (VICs) for microarray analysis. Differentially upregulated genes from the top of lesions and non-lesion fibrosa were related to lipid accumulation, inflammatory response, osteochondrogenesis, and ECM remodeling. An improved understanding of early CAVD microenvironment and VIC phenotypes lays the foundation to identify novel therapeutic targets.

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Cited By (2)

Year	Entry
2017	Blaser MC. The Role of C-Type Natriuretic Peptide Signaling in Aortic Valve Disease [PhD thesis]. University of Toronto; 2017.
2020	Maleki H. The Role of the Extracellular Matrix Microenvironment in Regulating Aortic Valve Cell Phenotypes [PhD thesis]. University of Toronto; 2020.