Excessive inflammation impairs heart regeneration in zebrafish breakdance mutant after cryoinjury. Issue 89 (June 2019)

• Record Type: Journal Article
• Authors: Xu, Shisan; Liu, Chichi; Xie, Fangjing; Tian, Li; Manno, Sinai HC.; Manno, Francis A.M.; Fallah, Samane; Pelster, Bernd; Tse, Gary; Cheng, Shuk Han
• Is Part Of: Fish & shellfish immunology. Issue 89(2019)
• Page Start: 117
• Page End: 126
• Publication Date: 2019-06
• Subjects: Excessive inflammation -- Heart regeneration -- Apoptosis -- Arrhythmia -- Immune therapy; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2019.03.058
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: Inflammation plays a crucial role in cardiac regeneration. Numerous advantages, including a robust regenerative ability, make the zebrafish a popular model to study cardiovascular diseases. The zebrafish breakdance ( bre ) mutant shares several key features with human long QT syndrome that predisposes to ventricular arrhythmias and sudden death. However, how inflammatory response and tissue regeneration following cardiac damage occur in bre mutant is unknown. Here, we have found that inflammatory response related genes were markedly expressed in the injured heart and excessive leukocyte accumulation occurred in the injured area of the bre mutant zebrafish. Furthermore, bre mutant zebrafish exhibited aberrant apoptosis and impaired heart regenerative ability after ventricular cryoinjury. Mild dosages of anti-inflammatory or prokinetic drugs protected regenerative cells from undergoing aberrant apoptosis and promoted heart regeneration in bre mutant zebrafish. We propose that immune or prokinetic therapy could be a potential therapeutic regimen for patients with genetic long QT syndrome who suffers from myocardial infarction. Highlights: Cardiac cryoinjury induces excessive inflammatory response in KCNH2 −/− mutant zebrafish breakdance. Cardiac cryoinjury induces aberrant apoptosis and more cell proliferation in zebrafish mutant breakdance. Heart regenerative ability is impaired in zebrafish mutant breakdance . Anti-inflammatory drugs and prokinetic drugs rescue the impaired heart regenerative capability in breakdance mutant fish.