COVID-19 and BRD4: a stormy and cardiotoxic bromo-romance

Abstract

Severe systemic inflammation in COVID-19 patients can lead to dysfunction of multiple organs, including the heart. Using an ex vivo cardiac organoid system, Mills et al discovered that inhibitors of the chromatin reader protein, bromodomain-containing protein 4, protect cardiomyocytes from COVID-associated “cytokine storm”. We briefly review these important findings and highlight the translational significance of the work.

Keywords

SARS-CoV-2 / COVID-19 / cytokine storm / bromodomain-containing protein 4 / diastolic dysfunction

References

[1] Szekely Y,Taieb P.Spectrum of cardiac manifestations in COVID-19: a systematic echocardiographic study.Circulation2020;142:342-53 PMCID:PMC7382541

[2] Bristow MR,Altman NL.Dynamic regulation of SARS-Cov-2 binding and cell entry mechanisms in remodeled human ventricular myocardium.JACC Basic Transl Sci2020;5:871-83 PMCID:PMC7314447

[3] Bailey AL,Greenberg L.SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis.JACC Basic Transl Sci2021;6:331-45 PMCID:PMC7909907

[4] Perez-Bermejo JA,Rockwood SJ.SARS-CoV-2 infection of human iPSC-derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19.Sci Transl Med2021;13 PMCID:PMC8128284

[5] Mills RJ,Fortuna PRJ et al.BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection.Cell2021;184:2167-82 e22 PMCID:PMC7962543

[6] Alexanian M,McKinsey TA.Epigenetic therapies in heart failure.J Mol Cell Cardiol2019;130:197-204 PMCID:PMC6850768

[7] Oladunni FS,Pino PA et al.Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice.Nat Commun2020;11:6122 PMCID:PMC7705712

[8] Nicholls SJ,Buhr KA.Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study.Cardiovasc Diabetol2021;20:13 PMCID:PMC7791841

[9] Kalantar-Zadeh K,Nicholls SJ.Effect of apabetalone on cardiovascular events in diabetes, CKD, and recent acute coronary syndrome: results from the BETonMACE randomized controlled trial.Clin J Am Soc Nephrol2021;16:705-16 PMCID:PMC8259488