Excessive inflammation impairs heart regeneration in zebrafish breakdance mutant after cryoinjury

Xu, Shisan; Liu, Chichi; Xie, Fangjing; Tian, Li; Manno, Sinai H. C.; Manno, Francis A. M.; Fallah, Samane; Pelster, Bernd; Tse, Gary; Cheng, Shuk Han

doi:10.1016/j.fsi.2019.03.058

Cited by 19 publications

(9 citation statements)

References 44 publications

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“…The amputation of the digit tip is followed by an early phase of inflammation and tissue histolysis with ECM remodeling that is essential for tissue healing and blastema formation. Then, the inflammation regresses and regeneration proceeds, as sustained inflammation may lead to regeneration failure (Gawriluk et al 2020; Xu et al 2019). This may be the case in the mutant blastema as we identified a number of genes related with inflammatory processes upregulated in the mutant blastema (Supplemental Fig 4C).…”

Section: Resultsmentioning

confidence: 99%

Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity

Castilla-Ibeas

Zdral

Galán

et al. 2022

Preprint

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Mammalian digit tip regeneration is linked to the presence of nail tissue, but a nail–explicit model is missing. Here, we report that nail–less double–ventral digits of ΔLARM1/2 mutants that lack limb–specific Lmx1b enhancers fail to regenerate. To separate the nail′s effect from the lack of DV polarity, we also interrogate double–dorsal double–nail digits and show that they regenerate. Thus, DV polarity is not a prerequisite for regeneration and the nail requirement is supported. Transcriptomic comparison between wild–type and non-regenerative ΔLARM1/2 mutant blastemas reveals differential upregulation of vascularization and connective tissue functional signatures in wild–type versus upregulation of inflammation in the mutant. These results, together with the finding of uniform Lmx1b expression in the wild–type blastema and in the dorsal dermis underneath the nail, indicate that, in addition of the nail′s effect, a direct role for Lmx1b in driving the progression of digit tip regeneration is likely.

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Section: Resultsmentioning

confidence: 99%

Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity

Castilla-Ibeas

Zdral

Galán

et al. 2022

Preprint

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“…However, sulfonylurea may also have anti-arrhythmic effects by inhibiting reentrant arrhythmias by a mechanism known as ischemic preconditioning (IPC), and thus reducing the risk of developing cardiac arrest (16), but it has been suggested that the effects of IPC are abolished in type 2 diabetes (23). Metformin has pleotropic effects with many cardiovascular bene ts as shown in basic science studies (24,25); it was found to be associated with a decreased QTc in animal models (26, 27), but no decrease in ventricular arrhythmic outcomes were re ected in clinical trials (28).…”

Section: Mechanism Underlying the Observationsmentioning

confidence: 99%

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared to metformin: a population-based cohort study

Tse

Lee

Hui

et al. 2022

Preprint

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Background: Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD) between metformin and sulfonylurea in patients with type 2 diabetes. Methods: Patients aged 40 years or older who were diagnosed with type-2 diabetes mellitus or prescribed anti-diabetic agents in Hong Kong between 1st January 2009 and 31st December 2009 were included and followed up till 31st December 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of VA/SCD. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. Results: The study cohort consisted of 5756 metformin users (48.00% male, age 68±11 years, mean follow-up 5.04±2.57 years) and 5756 sulfonylurea users (50.30% male, age 69±11 years, mean follow-up 5.04±2.54 years). Sulfonylurea was associated with higher risk of VA/SCD than metformin (hazard ratio 1.84 [1.56 - 2.16], p<0.001). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusion: Sulfonylurea use is associated with higher risk of VA/SCD than metformin in patients with type 2 diabetes.

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“…The combination of zebrafish genetic and regeneration models can also provide insights into how cardiac dysfunction alters regenerative capacity, and how therapeutic agents may be developed to improve this capacity. Cardiac regeneration is impaired in the zebrafish breakdance mutant LQTS model, associated with increased extracellular matrix (ECM) deposition and excessive inflammation (Xu et al, 2019). Although administration of inflammatory compounds such as dexamethasone or MMP inhibitors promotes scar resolution and regeneration in this model (Xu et al, 2019), timing and evolution of the immune response during regeneration is likely to be crucial in mediating regeneration (Lai et al, 2019), and zebrafish represent an excellent model to directly investigate how the immune response could be manipulated to promote regeneration in humans.…”

Section: Cardiac Disease Modelsmentioning

confidence: 99%

Zebrafish as a tractable model of human cardiovascular disease

Bowley

Kugler

Wilkinson

et al. 2021

British J Pharmacology

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Mammalian models including non-human primates, pigs and rodents have been used extensively to study the mechanisms of cardiovascular disease. However, there is an increasing desire for alternative model systems that provide excellent scientific value while replacing or reducing the use of mammals. Here we review the use of zebrafish, Danio rerio, to study cardiovascular development and disease. The anatomy and physiology of zebrafish and mammalian cardiovascular systems are compared, and we describe the use of zebrafish models in studying the mechanisms of cardiac (e.g. congenital heart defects, cardiomyopathy, conduction disorders, regeneration) and vascular (endothelial dysfunction and atherosclerosis, lipid metabolism, vascular ageing, neurovascular physiology and stroke) pathologies. We also review the use of zebrafish for studying pharmacological responses to cardiovascular drugs, and describe several features of zebrafish that make them a compelling model for in vivo screening of compounds for the treatment cardiovascular disease.

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Excessive inflammation impairs heart regeneration in zebrafish breakdance mutant after cryoinjury

Cited by 19 publications

References 44 publications

Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity

Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared to metformin: a population-based cohort study

Zebrafish as a tractable model of human cardiovascular disease

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