Harnessing Cardiac Regeneration as a Potential Therapeutic Strategy for AL Cardiac Amyloidosis
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Purpose of Review
Cardiac regeneration has received much attention as a possible means to treat various forms of cardiac injury. This review will explore the field of cardiac regeneration by highlighting the existing animal models, describing the involved molecular pathways, and discussing attempts to harness cardiac regeneration to treat cardiomyopathies.
Light chain cardiac amyloidosis is a degenerative disease characterized by progressive heart failure due to amyloid fibril deposition and light chain–mediated cardiotoxicity. Recent findings in a zebrafish model of light chain amyloidosis suggest that cardiac regenerative confers a protective effect against this disease.
Cardiac regeneration remains an intriguing potential tool for treating cardiovascular disease. Degenerative diseases, such as light chain cardiac amyloidosis, may be particularly suited for therapeutic interventions that target cardiac regeneration. Further studies are needed to translate preclinical findings for cardiac regeneration into effective therapies.
KeywordsAmyloidosis Light chain Cardiac regeneration Cardiomyopathy Zebrafish
Dr. Liao is supported by the National Institutes of Health (R01 grants HL 128135 and HL 132511). Dr. Alexander is supported the American Heart Association-Amos Medical Faculty Development Program.
Compliance with Ethical Standards
Conflict of Interest
Shaurya Joshi, Alessandro Evangelisti, and Ronglih Liao declare that they have no conflict of interest. Kevin Alexander has received a grant from Pfizer and participated on advisory boards for Alnylam and Eidos.
Human and Animal Rights and Informed Consent
The article does not contain any studies with human or animal subjects performed by any of the authors.
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 15.Soonpaa MH, Kim KK, Pajak L, Franklin M, Field LJ. Cardiomyocyte DNA synthesis and binucleation during murine development. Am J Phys. 1996;271(5 Pt 2):H2183–9.Google Scholar
- 17.• Mohamed TMA, Ang YS, Radzinsky E, Zhou P, Huang Y, Elfenbein A, et al. Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell. 2018;173(1):104–16 e12 This study suggests that a combination of cell cycle regulators can induce proliferation in post-mitotic mouse, rat, and human cardiomyocytes and that this strategy is beneficial in murine myocardial infarction models. PubMedPubMedCentralCrossRefGoogle Scholar
- 18.• Unno K, Oikonomopoulos A, Fujikawa Y, Okuno Y, Narita S, Kato T, et al. Alteration in ventricular pressure stimulates cardiac repair and remodeling. J Mol Cell Cardiol. 2019;133:174–87 This study suggests that proliferation of adult cardiac myocytes can be locally stimulated by changes in ventricular pressure, which can be leveraged for cardiac repair. PubMedCrossRefGoogle Scholar
- 27.• Das S, Goldstone AB, Wang H, Farry J, D'Amato G, Paulsen MJ, et al. A unique collateral artery development program promotes neonatal heart regeneration. Cell. 2019;176(5):1128–42 e18 This study identifies a mechanism involving CXCR4 and its ligand CXCL12 by which neonatal heart can form collateral arteries that contribute to cardiac regeneration. PubMedCrossRefGoogle Scholar
- 28.• Zhao L, Ben-Yair R, Burns CE, Burns CG. Endocardial notch signaling promotes cardiomyocyte proliferation in the regenerating zebrafish heart through wnt pathway antagonism. Cell Rep. 2019;26(3):546–54 e5 This study finds that during zebrafish heart regeneration, endocardial Notch signaling supports cardiomyocyte proliferation by attenuating myocardial Wnt signaling. PubMedPubMedCentralCrossRefGoogle Scholar
- 29.• Mahmoudi M, Yu M, Serpooshan V, Wu JC, Langer R, Lee RT, et al. Multiscale technologies for treatment of ischemic cardiomyopathy. Nat Nanotechnol. 2017;12(9):845–55 This review highlights major advancements in nanotechonology for the prevention and treatment of cardiovascular disease, particularly ischemic cardiomyopathy. PubMedPubMedCentralCrossRefGoogle Scholar
- 30.• Palmquist-Gomes P, Perez-Pomares JM, Guadix JA. Cell-based therapies for the treatment of myocardial infarction: lessons from cardiac regeneration and repair mechanisms in non-human vertebrates. Heart Fail Rev. 2019;24(1):133–42 This review discusses current approaches to study cardiac repair and regeneration using various animal models. PubMedCrossRefGoogle Scholar
- 34.•• Falk RH, Alexander KM, Liao R, Dorbala S. AL (light-chain) cardiac amyloidosis: a review of diagnosis and therapy. J Am Coll Cardiol. 2016;68(12):1323–41 This review discusses current and novel approaches to the diagnosis and treatment of light chain cardiac amyloidosis. PubMedCrossRefGoogle Scholar
- 42.Carrillo-Garcia C, Prochnow S, Simeonova IK, Strelau J, Holzl-Wenig G, Mandl C, et al. Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice. Development. 2014;141(4):773–83.PubMedPubMedCentralCrossRefGoogle Scholar
- 47.•• Mishra S, Joshi S, Ward JE, Buys EP, Mishra D, Mishra D, et al. Zebrafish model of amyloid light chain cardiotoxicity: regeneration versus degeneration. Am J Physiol Heart Circ Physiol. 2019;316(5):H1158–H66 This study describes a novel transgenic zebrafish model of light chain amyloidosis to gain insights into underlying disease mechanisms.PubMedCrossRefGoogle Scholar