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Review
. 2022 Jun 3:13:909801.
doi: 10.3389/fphar.2022.909801. eCollection 2022.

Mechanisms and Drug Therapies of Bioprosthetic Heart Valve Calcification

Shuyu Wen  1 , Ying Zhou  1 , Wai Yen Yim  1 , Shijie Wang  1 , Li Xu  1 , Jiawei Shi  1 , Weihua Qiao  1 , Nianguo Dong  1
Affiliations
Review

Mechanisms and Drug Therapies of Bioprosthetic Heart Valve Calcification

Shuyu Wen et al. Front Pharmacol. .

Abstract

Valve replacement is the main therapy for valvular heart disease, in which a diseased valve is replaced by mechanical heart valve (MHV) or bioprosthetic heart valve (BHV). Since the 2000s, BHV surpassed MHV as the leading option of prosthetic valve substitute because of its excellent hemocompatible and hemodynamic properties. However, BHV is apt to structural valve degeneration (SVD), resulting in limited durability. Calcification is the most frequent presentation and the core pathophysiological process of SVD. Understanding the basic mechanisms of BHV calcification is an essential prerequisite to address the limited-durability issues. In this narrative review, we provide a comprehensive summary about the mechanisms of BHV calcification on 1) composition and site of calcifications; 2) material-associated mechanisms; 3) host-associated mechanisms, including immune response and foreign body reaction, oxidative stress, metabolic disorder, and thrombosis. Strategies that target these mechanisms may be explored for novel drug therapy to prevent or delay BHV calcification.

Keywords: bioprosthetic heart valve; drug therapy; ectopic calcification; mechanisms; structural valve degeneration.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of bioprosthetic heart valve calcification. (A) Gross view of bioprosthetic heart valve calcification (arrowhead). (B) Low-energy radiography of bioprosthetic heart valve calcification (Delogne et al., 2007). (C) Ultrastructure of calcium deposits in the cell nuclei (arrow) (Schoen et al., 1994). (D) Scanned electron microscopy view of calcific loci depositing on collagen and elastin (Delogne et al., 2007). (E,F) calcospherulae arranged in concentric rings with and without a central core (Valente et al., 1985).
FIGURE 2
FIGURE 2
Schematic of the process of BHV calcification. Dead cells and cell debris, and elastin and GAGs degradation, and collagen crosslinks were present after GLUT treatment, providing calcium ions and the specific space structure for calcification. Serum protein and lipid infiltrated, cytokines, xenoantibodies secreted by B cells and thrombosis would activate macrophages and induce inflammatory response. Macrophages further secret MMPs and product ROS/RNS, leading to BHV calcification.
FIGURE 3
FIGURE 3
Risk factors and mechanisms of BHV calcification.
See this image and copyright information in PMC

References

    1. Amon R., Ben-Arye S. L., Engler L., Yu H., Lim N., Berre L. L., et al. (2017). Glycan Microarray Reveal Induced IgGs Repertoire Shift against a Dietary Carbohydrate in Response to Rabbit Anti-human Thymocyte Therapy. Oncotarget 8, 112236–112244. 10.18632/oncotarget.23096 - DOI - PMC - PubMed
    1. Antonini-Canterin F., Zuppiroli A., Popescu B. A., Granata G., Cervesato E., Piazza R., et al. (2003). Effect of Statins on the Progression of Bioprosthetic Aortic Valve Degeneration. Am. J. Cardiol. 92, 1479–1482. 10.1016/j.amjcard.2003.08.066 - DOI - PubMed
    1. Asselin J., Gibbins J. M., Achison M., Lee Y. H., Morton L. F., Farndale R. W., et al. (1997). A Collagen-like Peptide Stimulates Tyrosine Phosphorylation of Syk and Phospholipase C Gamma2 in Platelets Independent of the Integrin Alpha2beta1. Blood 89, 1235–1242. 10.1182/blood.v89.4.1235 - DOI - PubMed
    1. Badria A. F., Koutsoukos P. G., Mavrilas D. (2020). Decellularized Tissue-Engineered Heart Valves Calcification: what Do Animal and Clinical Studies Tell Us? J. Mater Sci. Mater Med. 31, 132. 10.1007/s10856-020-06462-x - DOI - PMC - PubMed
    1. Bailey M. T., Pillarisetti S., Xiao H., Vyavahare N. R. (2003). Role of Elastin in Pathologic Calcification of Xenograft Heart Valves. J. Biomed. Mater Res. A 66, 93–102. 10.1002/jbm.a.10543 - DOI - PubMed

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