Related Experiment Video

Updated: Jul 27, 2026

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

Cytokines are not upregulated in adriamycin-induced cardiomyopathy and heart failure

H Lou1, I Danelisen, P K Singal

  • 1Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Room 3022, 351 Tache Avenue, Winnipeg, Man., Canada R2H 2A6.

Journal of Molecular and Cellular Cardiology
|May 12, 2004
PubMed

Insights

Cytokine upregulation is not involved in Adriamycin-induced cardiomyopathy (AIC). Instead, heart failure in AIC may worsen due to decreased myocardial tumor necrosis factor-alpha (TNF-alpha).

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Inflammation Research

Background:

  • Heart failure is often associated with increased cytokine levels, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6).
  • Adriamycin-induced cardiomyopathy (AIC) is a significant clinical concern, and the role of cytokines in its pathogenesis requires further investigation.

Purpose of the Study:

  • To investigate the expression of key cytokines (TNF-alpha, IL-1beta, IL-6) in the myocardium and plasma during early and late stages of AIC in a rat model.
  • To determine if cytokine upregulation is a contributing factor to AIC or if other mechanisms are involved.

Main Methods:

  • Rats were induced with AIC, and both early and late stages were studied.
  • Myocardial gene expression of TNF-alpha, IL-1beta, and IL-6 was analyzed using DNA microarrays and RT-PCR.
  • Protein levels of these cytokines in plasma and myocardium were quantified using ELISA.
  • Lipopolysaccharide (LPS) was used as a positive control to validate cytokine induction.

Main Results:

  • In early AIC, myocardial IL-1beta mRNA increased, but TNF-alpha and IL-6 mRNA/protein levels remained unchanged or undetectable. Plasma cytokine levels were not elevated.
  • In late-stage AIC with confirmed heart failure, myocardial TNF-alpha mRNA and protein levels significantly decreased, while IL-1beta showed no significant change.
  • IL-6 was undetectable in myocardial tissue in both control and AIC groups, with no change in protein levels.
  • LPS treatment successfully induced significant increases in all three cytokines, validating the experimental system.

Conclusions:

  • Cytokine upregulation does not appear to be a primary mechanism in Adriamycin-induced cardiomyopathy.
  • A downregulation of myocardial TNF-alpha may contribute to or exacerbate heart failure in AIC.
  • These findings challenge the conventional understanding of cytokine involvement in chemotherapy-induced cardiotoxicity.

More Related Videos

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology10:41

Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology

Published on: January 23, 2021

Related Concept Videos

Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

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...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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...
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

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...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

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...