Regenerating a New Heart from the Programmed Ground: The Role of the Extracellular Matrix in Heart Regeneration

Abstract

The extracellular matrix (ECM) is a complex and dynamic three-dimensional network that functions as an architectural scaffold to maintain cardiac homeostasis. Important biochemical and mechanical signals associated with cell‒cell communication are provided via the reciprocal interaction between cells and the ECM. By converting mechanical cues into biochemical signals, the ECM regulates many cell processes, including migration, adhesion, growth, differentiation, proliferation, and apoptosis. Moreover, the ECM facilitates the replacement of dead cells and preserves the structural integrity of the heart, making it essential in conditions such as myocardial infarction and other pathological states. When there is excessive deposition of ECM or abnormal production of ECM components, the heart undergoes fibrosis, leading to cardiac dysfunction and heart failure. However, emerging evidence suggests that the ECM may contribute to heart regeneration following cardiac injury. The present review offers a complete overview of the existing information and novel discoveries regarding the involvement of the ECM in heart regeneration from both mechanical and biochemical perspectives. Understanding the ECM and its involvement in mechanotransduction holds significant potential for advancing therapeutic approaches in heart repair and regeneration.

Note:
Funding declaration: This work was supported by the Zhejiang Provincial Natural Science Foundation (LR21H020001 to HM), the Zhejiang Provincial Medical and Health Technology Project (2023RC020 to SY), and the National Natural Science Foundation of China (82070252 to HM).

Conflict of Interest: The authors declare that there is no conflict of interest.

Keywords: extracellular matrix, Fibroblasts, Heart failure, heart regeneration, mechanics