The pathomechanism of human myxomatous valvular degeneration at the mechanical and cellular level

³ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China

^*Correspondence: nianguodonguh@163.com (Nianguo Dong); mingkuizhanghx@163.com (Mingkui Zhang)
^† These authors contributed equally.
Academic Editor: Brian Tomlinson

Rev. Cardiovasc. Med. 2021, 22(2), 513–519; https://doi.org/10.31083/j.rcm2202059

Submitted: 11 April 2021 | Revised: 7 May 2021 | Accepted: 11 June 2021 | Published: 30 June 2021

(This article belongs to the Special Issue State-of-the-Art Cardiovascular Medicine in Asia 2021)

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

The purpose of this study was to explore the pathomechanism of human myxomatous valve degeneration by investigating changes in the phenotype of valvular cells, the metabolism of the extracellular matrix and their mechanical properties. Mitral valve specimens were harvested from patients who had undergone valve replacement, and divided into two groups: patients with a myxomatous mitral valve and a control group. Histological investigation showed that the morphology of the extracellular matrix was looser and less coordinated in myxomatous valves than in controls. $\alpha$ -SMA ( $\alpha$ -smooth muscle actin) and Vimentin were positive and DNA (deoxyribonucleic acid) assay of leaflets and expression of SMemb (embryonic smooth muscle myosin heavy chain), MMP-13 (matrix Metalloproteinases-13), MMP-1 mRNA (messenger Ribonucleic Acid) of the myxomatous valves were increased while the hydroxyproline content, expression of TIMP-1 (tissue inhibitor of metalloproteinase-1) mRNA and mechanical properties were decreased compared with controls. Compared to the quiescent interstitial cells in non-myxomatous valves, interstitial cells in myxomatous valves exhibit myofibroblast activation and express excessive levels of matrix metalloproteinases. The balance between MMP/TIMP was disrupted. We conclude that overactivation of VICs (Valvular interstitial cells) and the imbalance of MMP/TIMP could be important features of the pathomechanism of myxomatous mitral valve degeneration.

Keywords

Myxomatous mitral valve

Degeneration

Valvular interstitial cell

Extracellular matrix

Mechanical property

Figures

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Fig. 1.

Histologic examination of valve leaflets. (A) Control group: Cells were distributed in all three layers, of an integrated and compact three-tier structure (fibrous layer, sponge layer, and ventricular layer) which was interconnected by dense fibrous tissue. (B) Diseased group: The number of cells increased slightly. The three-tier structure was still intact, however, fibrous tissue was loose and disordered, and the sponge layer was broader with more voids (A and B: hematoxylin and eosin; original magnification $\times{}$ 20).

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Rev. Cardiovasc. Med. Print ISSN 1530-6550 Electronic ISSN 2153-8174