Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity

Area of Science:

• Cardiology
• Oncology
• Fibrosis Research

Background:

• Anthracyclines are vital chemotherapy drugs but cause dose-dependent cardiotoxicity.
• Traditionally, cardiotoxicity was linked to direct cardiomyocyte damage.
• Emerging research implicates cardiac fibroblasts (CFs) in anthracycline cardiotoxicity.

Purpose of the Study:

• To review the role of cardiac fibroblasts in anthracycline-induced cardiotoxicity.
• To examine doxorubicin's effects on CFs across different injury phases.
• To highlight CFs' contribution to fibrosis, senescence, and inflammation.

Main Methods:

• Literature review focusing on anthracyclines, doxorubicin (DOX), and cardiac fibroblasts.
• Analysis of DOX's impact on CFs and extracellular matrix remodeling.
• Examination of temporal aspects of anthracycline cardiotoxicity.

Main Results:

• DOX activates CFs, promoting extracellular matrix remodeling and fibrosis.
• CF-induced senescence and collagen production exacerbate myocardial inflammation and dysfunction.
• Anthracycline cardiotoxicity presents acutely, subacutely, or chronically, with late-stage damage often irreversible.

Conclusions:

• Cardiac fibroblasts play a critical role in anthracycline cardiotoxicity.
• Understanding CF mechanisms offers potential therapeutic targets.
• Preventing or mitigating CF activation could protect against heart damage from chemotherapy.