Section 1
Basic Sciences
Section Editor: Bhagirath Raghuraman
Tarbit E, Singh I, Peart JN, et al. Biomarkers for the identification of cardiac fibroblast and myofibroblast cells.
Heart Fail Rev. 2019;24(1):1-15.
Abstract*
In heart repair and function, the importance of cardiac fibroblast and myofibroblast cells has been recognized by several experimental researches. In normal healthy heart, there is a central role of the cardiac fibroblast in the electrical, chemical, and structural aspects within the heart. It is interesting to note that in the development of heart failure, transformation of the cardiac fibroblast cells to the cardiac myofibroblast cells is thought to play an important part. It is always a challenge to differentiate between the two cells types. As myofibroblast cells are expressed only in failing or stressed heart, therefore, a better understanding of the cell function can aid in identifying therapies that help in the repair of damaged heart. This article will give an outline of what is presently known regarding the physiological and pathological roles within the heart, cardiac fibroblasts, and myofibroblasts; their pathological and physiological roles within the heart; and the causes of the transition of fibroblasts into myoblasts. Potential markers that are available for characterizing these cells were also reviewed and it was observed that there is not a single cell-specific marker that delineates fibroblast cell or myofibroblast cell. Vimentin is commonly used for characterizing the cells of fibroblast origin. Discoidin domain receptor 2 (DDR2) is used to distinguish cardiac fibroblasts; whereas, myofibroblasts can be identified using α-smooth muscle actin. A known cytokine, transforming growth factor beta-1 (TGF-β1), is well known for causing transformation of the cardiac fibroblasts to the myofibroblasts. In this review, clinical treatments that can reduce or inhibit the actions of TGF-β1 along with its contribution to heart failure and cardiac fibrosis are also discussed.
“We need to identify potential cell-specific markers for cardiac fibroblast and myofibroblast cells, which will allow for new potential targets for the treatment of heart failure”
COMMENT
The basic problem is that there is no single cell-specific marker exists, which delineates fibroblast cells or myofibroblast cells. By using discoidin domain receptor 2 (DDR2), cardiac fibroblasts can be recognized; whereas, myofibroblasts can be identified using α-smooth muscle actin. Presently, periostin is evolving as a potential marker for myofibroblasts. A combination of presently available markers is recommended to be used for studying myofibroblasts and fibroblasts as accurately as possible. Implementing proteomics research in the future may help to identify cardiac biomarkers for heart failure (HF) and would enable a more tailored treatment approach. It is well known that transforming growth factor beta-1 (TGF-β1) mediates the activation of fibroblast cells and their transformation to myofibroblasts and that both cell types have a contribution in fibrosis and impaired heart function.
Modifying TGF-β1 may pave the way to modulate HF. Cardiac fibroblast cells have no cell-specific marker for identification, and as a consequence, research within its field is often challenging. Under various conditions, cardiac fibroblasts may be triggered to transform into the myofibroblast cells. There is a major requirement to identify the potential cell-specific markers for cardiac fibroblast and myofibroblast cells that will allow for new potential targets in the treatment of HF. Most of the current available treatment targets that are available for cardiac fibrosis/HF are broad-acting; these are not recommended for long-term use because they can affect the quality of life of patient because of unwanted side effects. In the future, microRNA-130a and TGF-β have potential as new targets in treatment of HF and cardiac fibrosis. However, there is need for further research to be conducted.