Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder
that ultimately causes gradual narrowing of the left ventricular outflow orifice with
ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation
is the hallmark pathology defining this process; however, fibrotic extracellular matrix
(ECM) remodeling that leads to extensive deposition of fibrous connective tissue
and distortion of the valvular microarchitecture similarly has major biomechanical and
functional consequences for heart valve function. Significant advances have been made
to unravel the complex mechanisms that govern these active, cell-mediated processes,
yet the interplay between fibrosis and calcification and the individual contribution to
progressive extracellular matrix stiffening require further clarification. Specifically, we
discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns
in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3)
imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5)
molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse
remodeling. This review explores our current understanding of the cellular and molecular
drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84542 |
| Date | 04 April 2023 |
| Creators | Büttner, Petra, Feistner, Lukas, Lurz, Philipp, Thiele, Holger, Hutcheson, Joshua D., Schlotter, Florian |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2297-055X, 660797 |
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