Related Experiment Video
Updated: Nov 22, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Cardiotoxic effects of angiogenesis inhibitors
Stephen J H Dobbin1, Mark C Petrie1, Rachel C Myles1
1BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, United Kingdom, G12 8TA.
Abstract:
The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the 'on-target' effects of VEGF inhibition or 'off-target' effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.
Insights
Vascular endothelial growth factor inhibitors (VEGFIs) improve cancer survival but can cause heart problems like heart failure. Further research is needed to understand and manage these cardiovascular toxicities.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Cancer therapies, including angiogenesis inhibitors, have improved patient survival.
- Angiogenesis inhibitors, particularly vascular endothelial growth factor inhibitors (VEGFIs), are linked to significant cardiovascular toxicities.
- These toxicities can compromise cancer treatment and increase long-term morbidity and mortality.
Purpose of the Study:
- To review the cardiovascular toxicities associated with VEGFIs.
- To explore the potential mechanisms underlying VEGFI-induced cardiac dysfunction.
- To highlight the need for further research and clinical strategies.
Main Methods:
- Literature review of pre-clinical and clinical studies on VEGFI cardiovascular effects.
- Analysis of mechanisms including direct myocardial insult, vascular damage, and on-target/off-target effects.
- Examination of specific toxicities such as hypertension, left ventricular systolic dysfunction (LVSD), heart failure, thromboembolism, and arrhythmia.
Main Results:
- VEGFIs are associated with hypertension, LVSD, heart failure, thromboembolism, QTc prolongation, and arrhythmia.
- Mechanisms involve direct and secondary myocardial insults, potentially through on-target or off-target effects.
- Similar mechanisms may contribute to right ventricular dysfunction and arrhythmias.
Conclusions:
- VEGFIs present a complex cardiovascular risk profile, including heart failure and arrhythmias.
- Understanding the precise mechanisms of VEGFI cardiotoxicity is crucial for developing effective management strategies.
- Further pre-clinical and clinical studies are essential to guide therapeutic interventions and surveillance for cardiovascular complications.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:26Heart Failure Drugs: Inotropic Agents
01:24Regulation of Angiogenesis and Blood Supply
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...