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Review
. 2022 May 27;23(6):196.
doi: 10.31083/j.rcm2306196. eCollection 2022 Jun.

The Heart in Fabry Disease: Mechanisms Beyond Storage and Forthcoming Therapies

Maurizio Pieroni  1 , Michele Ciabatti  1 , Francesca Graziani  2 , Antonia Camporeale  3 , Elisa Saletti  1 , Rosa Lillo  2 , Stefano Figliozzi  4 , Leonardo Bolognese  1
Affiliations
Review

The Heart in Fabry Disease: Mechanisms Beyond Storage and Forthcoming Therapies

Maurizio Pieroni et al. Rev Cardiovasc Med. .

Abstract

In patients with Fabry disease (FD), cardiovascular involvement is the main cause of death and reduction of quality of life. Left ventricular hypertrophy mimicking hypertrophic cardiomyopathy is the main feature of FD cardiac involvement although glycolipid storage occurs in all cardiac cellular types. Accumulation of lysosomal globotriasylceramide represents the main mechanism of cardiac damage in early stages, but secondary pathways of cellular and tissue damage, triggered by lysosomal storage, and including altered energy production, inflammation and cell death, contribute to cardiac damage and disease progression. These mechanisms appear prominent in more advanced stages, hampering and reducing the efficacy of FD-specific treatments. Therefore, additional cardiovascular therapies are important to manage cardiovascular symptoms and reduce cardiovascular events. Although new therapies targeting lysosomal storage are in development, a better definition and comprehension of the complex pathophysiology of cardiac damage in FD, may lead to identify new therapeutic targets beyond storage and new therapeutic strategies.

Keywords: Fabry disease; autophagy; left ventricular hypertrophy; lysosomal storage; myocardial inflammation; unfolded protein response.

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Conflict of interest statement

Maurizio Pieroni: advisory board honoraria from Amicus Therapeutics and Sanofi Genzyme; he has received speaker honoraria from Amicus Therapeutics, Sanofi Genzyme, and Takeda. Francesca Graziani: Honoraria for presentations, board meetings and travel support from Amicus Therapeutics, Sanofi-Genzyme and Takeda. Antonia Camporeale: Honoraria for presentations and board meetings from Amicus Therapeutics, Sanofi-Genzyme and Takeda. Research grant from Amicus Therapeutics. Rosa Lillo: Honoraria for board meetings and travel support from Amicus Therapeutics, Sanofi-Genzyme and Takeda. Maurizio Pieroni is serving as one of the Editorial Board members/Guest editors of this journal. We declare that Maurizio Pieroni had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Sophie Mavrogeni. Other authors have no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Classic pathophysiology of cardiac involvement in Fabry disease. In blue the main pathophysiologic mechanisms; in red the main clinical manifestations.
Fig. 2.
Fig. 2.
Additional secondary cellular and tissue pathways of damage triggered by lysosomal storage. ER, endoplasmic reticulum.
Fig. 3.
Fig. 3.
Schematic representation of relevance of Gb3 storage and secondary mechanisms and clinical impact of FD-specific and organ-specific treatments, according to progression of cardiac involvement and age. With the progression of cardiac damage the relevance of Gb3 storage decreases while secondary pathaways become prominent. Accordingly the impact of therapies targeting Gb3 storage gradually decrease with the need of additional organ specific treatments targeting secondary pathways.
See this image and copyright information in PMC

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