# Cardio-Vascular Extracellular Matrix: The Unmet Enigma

## TL;DR

The heart's extracellular matrix is a key player in cardiovascular health and disease, influencing heart function and fibrosis.

## Contribution

The paper highlights the ECM's active role in heart function and disease, emphasizing its importance in new diagnostics and therapies.

## Key findings

- ECM regulates mechanical, electrical, and biochemical signaling in the heart.
- Myocardial fibrosis driven by ECM disruption causes heart failure and arrhythmias.
- ECM changes vary with age and sex, affecting cardiovascular disease susceptibility.

## Abstract

The cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age- and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations.