Cardiac Fibroblasts in Extracellular Matrix Homeostasis and Remodeling

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Fibrosis Research

Background:

• Cardiac fibroblasts, once considered passive support cells, are now known as dynamic regulators of heart function.
• Fibroblast heterogeneity and activation into myofibroblasts are critical in cardiac remodeling and fibrosis.
• Multiple signaling pathways govern fibroblast activation and extracellular matrix remodeling.

Purpose of the Study:

• To synthesize current knowledge on cardiac fibroblast mechanisms in myocardial homeostasis and disease.
• To highlight the role of fibroblast heterogeneity and activation in pathological cardiac remodeling.
• To identify key signaling pathways controlling fibroblast phenotype and extracellular matrix turnover.

Main Methods:

• This review synthesizes existing literature on cardiac fibroblast biology.
• It analyzes molecular and cellular mechanisms driving fibroblast activation and function.
• The review integrates findings on signaling pathways influencing fibroblast behavior.

Main Results:

• Cardiac fibroblasts are central mediators of extracellular matrix turnover, paracrine signaling, and electromechanical coupling.
• Fibroblast activation into myofibroblasts drives wound repair but also maladaptive fibrosis.
• Complex signaling networks, including TGF-β/SMAD and RAAS, control fibroblast activation and outcomes.

Conclusions:

• Resident cardiac fibroblasts are dominant drivers of extracellular matrix remodeling and fibrosis.
• Further research is needed on fibroblast plasticity, arrhythmogenesis, and cardiometabolic remodeling.
• Targeted antifibrotic interventions require understanding context-dependent fibroblast functions for improved cardiovascular disease outcomes.