Related Experiment Video
Updated: Nov 10, 2025
09:53
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
652
BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection
Richard J Mills1, Sean J Humphrey2, Patrick R J Fortuna1
1QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia.
Cell
|April 3, 2021
Summary
COVID-19 causes cardiac injury via inflammation. Bromodomain and extraterminal family inhibitors (BETi) show promise in preventing heart dysfunction and death in models, offering potential therapeutic strategies.
Area of Science:
- Cardiology
- Virology
- Molecular Biology
Background:
- COVID-19 is linked to cardiac injury and mortality.
- Mechanisms include direct viral infection or inflammation-induced cardiac dysfunction.
- Identifying therapeutic targets is crucial for managing COVID-19's cardiac impact.
Purpose of the Study:
- To elucidate the mechanisms of COVID-19-induced cardiac dysfunction.
- To identify potential cardio-protective drugs against COVID-19.
Main Methods:
- Utilized human cardiac organoids (hCOs) and K18-hACE2 mouse models.
- Employed phosphoproteomics and single nuclei RNA sequencing.
- Investigated the effects of inflammatory stimuli and BET inhibitors.
Main Results:
- A "cytokine-storm" (interferon gamma, interleukin 1β, poly(I:C)) induced diastolic dysfunction.
- Bromodomain-containing protein 4 activation and a viral response were observed in hCOs and mouse models.
- BET inhibitors (BETi) restored cardiac function in hCOs and prevented mortality in mice.
- BETi reduced viral gene transcription, ACE2 expression, and cardiomyocyte infection.
Conclusions:
- BETi, including apabetalone, effectively counteract COVID-19-induced cardiac dysfunction and mortality.
- BETi represent promising therapeutic candidates for preventing cardiac damage in COVID-19 patients.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
653
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
653
01:14Myocarditis III: Medical Management
58
Myocarditis: Comprehensive Medical ManagementMyocarditis, the heart muscle inflammation, requires a comprehensive medical management strategy that addresses the underlying cause, provides supportive care, manages symptoms, and reduces cardiac workload.Infections and Autoimmune CausesAdminister appropriate antimicrobial therapy when an infectious agent causes myocarditis. For instance, penicillin treats infections caused by Group A Streptococcus. In cases where autoimmune processes are...
58
01:21Myocarditis I: Introduction
139
Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
139
01:22Heart Failure Drugs: β-Blockers
548
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
548
01:26Heart Failure Drugs: Inotropic Agents
914
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
914
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
172
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
172