Cardiac fibrosis
Pro Research Analysisby 
Searched over 200M research papers for "cardiac fibrosis"
Cardiac Fibrosis: Definition and Clinical Impact
Cardiac fibrosis is the excessive buildup of extracellular matrix (ECM) proteins in the heart, leading to stiffening of the myocardium, impaired heart function, and increased risk of arrhythmias and heart failure. It is a common feature in many heart diseases, including myocardial infarction, heart failure (both with reduced and preserved ejection fraction), genetic cardiomyopathies, and diabetic heart disease. The fibrotic process can be reparative, helping to maintain structural integrity after injury, or maladaptive, contributing to disease progression and poor clinical outcomes 1234789.
Cellular and Molecular Mechanisms of Cardiac Fibrosis
Role of Cardiac Fibroblasts and Myofibroblasts
Cardiac fibroblasts are the main cells responsible for ECM production in the heart. After injury or under stress, these cells become activated and transform into myofibroblasts, which are highly proliferative and secrete large amounts of collagen and other matrix proteins. This transformation is central to the development of fibrotic scars and adverse remodeling of the heart 124567.
Involvement of Other Cardiac and Immune Cells
Other cell types, such as cardiomyocytes, endothelial cells, pericytes, macrophages, lymphocytes, and mast cells, also contribute to fibrosis. They do so by releasing proteases, fibrogenic mediators, and matricellular proteins, or by directly influencing fibroblast behavior through cell-to-cell contact 246.
Key Signaling Pathways and Mediators
Fibrogenic growth factors (like TGF-β and PDGFs), cytokines (such as TNF-α, IL-1, IL-6, IL-10, and IL-4), and neurohumoral pathways activate signaling cascades in fibroblasts, leading to increased ECM production. These signals are transmitted through cell surface receptors, including integrins and cytokine receptors, and involve both Smad-dependent and independent pathways 125910. Mechanical stress sensed by fibroblasts also triggers fibrogenic responses, especially in conditions like pressure overload 12.
Types and Consequences of Cardiac Fibrosis
There are different types of cardiac fibrosis, including reparative (following cell death, such as after a heart attack) and reactive (in response to chronic stress, aging, or metabolic dysfunction). Both types can lead to stiffening of the heart, reduced ejection fraction, impaired electrical conduction, and increased risk of arrhythmias and heart failure 1234789.
Diagnosis and Clinical Assessment
Non-invasive imaging techniques and circulating biomarkers are being developed and refined to better diagnose and characterize cardiac fibrosis. Improved patient phenotyping is important for understanding the heterogeneity of fibrosis and for guiding personalized treatment strategies 389.
Therapeutic Strategies and Challenges
Currently, there are no curative treatments for cardiac fibrosis. Existing therapies for heart failure may have some antifibrotic effects, but specific antifibrotic drugs are lacking. Promising strategies under investigation include targeting fibroblast activation, using chimeric antigen receptor (CAR-T) cell therapy, direct reprogramming of cells, and advanced drug delivery systems such as nanoparticles and exosomes. However, the complexity and reparative nature of fibrosis make it challenging to develop effective and safe treatments 246810.
Conclusion
Cardiac fibrosis is a major contributor to heart dysfunction and poor outcomes in a wide range of heart diseases. It involves complex interactions between multiple cell types and signaling pathways, leading to excessive ECM deposition and structural remodeling. While significant progress has been made in understanding the mechanisms of cardiac fibrosis, effective targeted therapies remain an urgent unmet need. Ongoing research into the molecular pathways, diagnostic tools, and novel therapeutic approaches holds promise for better management and treatment of cardiac fibrosis in the future 12345678+2 MORE.
Sources and full results
Most relevant research papers on this topic