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Dynamic interactions between myocytes, fibroblasts, and extracellular matrix
Indroneal Banerjee1, Krishna Yekkala, Thomas K Borg
1Cell and Developmental Biology and Anatomy, University of South Carolina, School of Medicine, Columbia, SC 29208, USA.
Insights
Cardiac fibroblasts dynamically interact with the extracellular matrix and myocytes, influencing heart function through mechanical, chemical, and electrical signals. Their numbers change significantly, impacting cardiac health.
Area of Science:
- Cardiovascular Biology
- Cellular Cardiology
- Cardiac Extracellular Matrix
Background:
- Cardiac function relies on intricate interactions between diverse cell types and the extracellular matrix (ECM).
- Mechanical, chemical, and electrical signals coordinate cellular and non-cellular components within the heart.
- While cardiomyocyte numbers are stable, cardiac fibroblast populations fluctuate significantly during development and disease.
Purpose of the Study:
- To explore the dynamic role of cardiac fibroblasts in cardiac function.
- To elucidate the signaling pathways and cellular interactions governing fibroblast behavior.
- To discuss how quantitative changes in signals affect cardiac form and function.
Main Methods:
- Utilized fluorescence-activated cell sorting to quantify cell populations.
- Investigated intercellular communication via cadherins and connexins.
- Examined cell-ECM interactions through integrins.
- Analyzed signaling pathways involving angiotensin II (Ang II) and cytokines.
Main Results:
- Cardiac fibroblast numbers change dramatically compared to relatively constant myocyte numbers.
- Fibroblasts form an interconnected network, communicating with each other, the ECM, and myocytes.
- Angiotensin II and cytokine signaling create feedback loops affecting fibroblast activity and ion channel function.
Conclusions:
- Cardiac fibroblasts are crucial, dynamic components of the heart, significantly influencing cardiac function.
- Intercellular and cell-matrix signaling pathways, particularly involving Ang II, regulate fibroblast behavior.
- Understanding these quantitative signal changes is key to comprehending alterations in cardiac form and function.
Abstract:
Cardiac function is determined by the coordinated and dynamic interaction of several cell types together with components of the extracellular matrix (ECM). This interaction is regulated by mechanical, chemical, and electrical signals between the cellular and noncellular components of the heart. Recent studies using fluorescence-activated cell sorting indicate that the number of myocytes remains relatively constant during development and disease, whereas the number of fibroblasts and other cell types can change dramatically. Cardiac fibroblasts appear to have different origins at different stages of development and fluctuate in response to a variety of physiological signals. Fibroblasts form a network of cells that are connected to each other via specific cadherins and connexins, to the ECM via integrins, and to myocytes by a variety of receptors, including connexins. Examples of the integration of signals include the role of angiotensin II (Ang II), which stimulates mechanical contraction of fibroblasts, as well as cytokine signaling. Cytokine signaling alters connexin and K(+) channel activation, which in turn is regulated by Ang II, essentially forming a feedback loop. Quantitative changes in mechanical, chemical, and electrical signals that can alter the overall cardiac form and function will be discussed here.
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