Cardiac Remodeling and Fibrosis Mechanisms

Cardiac remodelling denotes the structural, cellular and molecular alterations that occur in the heart in response to injury or chronic stress. These changes encompass cardiomyocyte hypertrophy, loss of contractile cells, expansion of the interstitial compartment and accumulation of extracellular matrix components. Fibrosis, the excessive deposition of collagen and related macromolecules by activated fibroblasts and myofibroblasts, stiffens the myocardial parenchyma, impairs electrical conduction and accelerates progression to heart failure. Central to this process is a coordinated interplay between inflammatory mediators, mechanical forces and paracrine signalling pathways such as transforming growth factor-β and Wnt/β-catenin. Emerging evidence from genetic lineage tracing, transcriptomic profiling and advanced imaging has deepened our understanding of the cellular origin and plasticity of fibrogenic cell types, the temporal dynamics of reparative versus reactive fibrosis, and the pivotal role of non-cardiomyocyte populations including macrophages and vascular cells. A global research effort now focuses on modulating fibroblast activation, targeting profibrotic signalling cascades and harnessing endogenous regenerative programmes to attenuate maladaptive remodelling and preserve cardiac function.

Research from Nature Portfolio

Genetic lineage tracing has defined periostin-expressing myofibroblasts as the principal effector cells in scar formation and adaptive repair following myocardial infarction. By employing inducible Cre-recombinase strategies, investigators demonstrated that these myofibroblasts arise from a resident fibroblast pool marked by the Tcf21 lineage rather than from endothelial or immune sources. Ablation of periostin+ cells reduced collagen deposition and scar size, while surviving myofibroblasts reverted to a less activated state upon injury resolution. This work established the myofibroblast as a discrete, plastic cell type essential for both reparative healing and the chronic fibrotic response.

Cardiac Remodeling and Fibrosis Mechanisms publication trend

The graph below shows the total number of articles in cardiac remodeling and fibrosis mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Cardiac fibroblast: Interstitial cell responsible for synthesis and turnover of extracellular matrix in the myocardium.

Myofibroblast: Activated fibroblast phenotype characterised by expression of contractile proteins and high collagen secretion.

Extracellular matrix: Network of collagen, glycoproteins and proteoglycans that provides structural support to cardiac tissue.

Fibrosis: Pathological accumulation of extracellular matrix leading to tissue stiffening and functional impairment.

Cardiac remodelling: Structural and functional adaptation of the heart in response to injury or chronic haemodynamic load.

Transforming growth factor-β (TGF-β): Cytokine that orchestrates fibroblast activation and matrix deposition during repair and fibrosis.

Wnt signalling: Developmental pathway implicated in fibroblast differentiation, scar maturation and tissue regeneration.

References

1. TEA domain transcription factor 1 (TEAD1) induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway. Signal Transduction and Targeted Therapy (2024).
2. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nature Communications (2016).
3. Signaling pathways and targeted therapy for myocardial infarction. Signal Transduction and Targeted Therapy (2022).