Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
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...
Heart Failure I: Introduction01:27

Heart Failure I: Introduction

Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. 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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Association of stromal cell-derived factor 1α and interferon-γ-induced protein 10 with Fontan pathophysiology.

Canadian journal of physiology and pharmacology·2026
Same author

Lipidomic remodeling is associated with hemodynamic severity in calcific aortic valve stenosis.

American journal of physiology. Heart and circulatory physiology·2026
Same author

The Cardioprotective Effects of Empagliflozin with and Without ACE Inhibition in Chemotherapy-Induced Cardiotoxicity.

Biomedicines·2026
Same author

Regulation of Endoplasmic Reticulum Stress by Empagliflozin in Doxorubicin-Induced Cardiotoxicity in Rats.

Journal of cellular and molecular medicine·2026
Same author

Can flaxseed "milk" prevent anthracycline mediated cardiotoxicity in women with breast cancer (CANFLAX-BC)?

Cardio-oncology (London, England)·2026
Same author

Heart in the Crossfire: Immune Checkpoint Inhibitor-Mediated Cardiotoxicity.

The Canadian journal of cardiology·2025

Related Experiment Video

Updated: May 27, 2026

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
13:59

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Published on: August 18, 2023

Trastuzumab-induced cardiac dysfunction: A 'dual-hit'.

Matthew Zeglinski1, Ana Ludke, Davinder S Jassal

  • 1Department of Physiology, Institute of Cardiovascular Sciences, St Boniface Research Centre;

Experimental and Clinical Cardiology
|November 9, 2011
PubMed
Summary

Trastuzumab (Trz) and doxorubicin (DOX) can cause heart damage, primarily through oxidative stress. Understanding this dual-hit mechanism is key to developing new cardioprotective strategies against drug-induced cardiomyopathy.

Keywords:
DoxorubicinEpidermal growth factorHeart failureOxidative stressRenin-angiotensin system

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Related Experiment Videos

Last Updated: May 27, 2026

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
13:59

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Published on: August 18, 2023

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • Trastuzumab (Trz), a monoclonal antibody targeting HER2, is used in breast cancer treatment.
  • Trz and doxorubicin (DOX) can cause cardiotoxicity, especially when used together.
  • Oxidative stress is a significant contributing factor to this drug-induced cardiac dysfunction.

Purpose of the Study:

  • To review evidence linking oxidative stress to DOX and Trz-induced cardiotoxicity.
  • To explore the 'dual-hit' mechanism involving Trz and its impact on cardiomyocyte survival pathways.
  • To discuss potential cardioprotective strategies against drug-induced cardiomyopathy.

Main Methods:

  • Review of existing scientific literature on Trastuzumab (Trz) and Doxorubicin (DOX) cardiotoxicity.
  • Analysis of mechanisms contributing to oxidative stress and cardiac damage.
  • Discussion of potential therapeutic interventions and preventative measures.

Main Results:

  • Oxidative stress arises from increased reactive oxygen species (ROS) and decreased antioxidant defenses.
  • Trz exacerbates cardiomyocyte damage via inhibition of neuregulin-1 signaling and activation of NADPH oxidase.
  • This 'dual-hit' mechanism significantly increases ROS production, leading to cardiac dysfunction.

Conclusions:

  • A comprehensive understanding of DOX and Trz-induced cardiotoxicity mechanisms is crucial.
  • Potential cardioprotective strategies include ACE inhibitors, beta-blockers, and antioxidants.
  • Further research is needed to develop effective preventive therapies for drug-induced cardiomyopathy.