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Review
. 2014 May:70:92-9.
doi: 10.1016/j.yjmcc.2014.01.008. Epub 2014 Jan 26.

Myocardial fibroblast-matrix interactions and potential therapeutic targets

Edie C Goldsmith  1 , Amy D Bradshaw  2 , Michael R Zile  2 , Francis G Spinale  3
Affiliations
Review

Myocardial fibroblast-matrix interactions and potential therapeutic targets

Edie C Goldsmith et al. J Mol Cell Cardiol. 2014 May.

Abstract

The cardiac extracellular matrix (ECM) is a dynamic structure, adapting to physiological and pathological stresses placed on the myocardium. Deposition and organization of the matrix fall under the purview of cardiac fibroblasts. While often overlooked compared to myocytes, fibroblasts play a critical role in maintaining ECM homeostasis under normal conditions and in response to pathological stimuli assume an activated, myofibroblast phenotype associated with excessive collagen accumulation contributing to impaired cardiac function. Complete appreciation of fibroblast function is hampered by the lack of fibroblast-specific reagents and the heterogeneity of fibroblast precursors. This is further complicated by our ability to dissect the role of myofibroblasts versus fibroblasts in myocardial in remodeling. This review highlights critical points in the regulation of collagen deposition by fibroblasts, the current panel of molecular tools used to identify fibroblasts and the role of fibroblast-matrix interactions in fibroblast function and differentiation into the myofibroblast phenotype. The clinical potential of exploiting differences between fibroblasts and myofibroblasts and using them to target specific fibroblast populations is also discussed. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."

Keywords: Discoidin Domain Receptor; Extracellular matrix; Fibroblast; Integrin; Myofibroblast; Transformation.

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Figures

Figure 1
Figure 1. The Cardiac Fibroblast
As shown in this figure, cardiac fibroblasts arise from divergent sources during development and in response to pathological insult. In response to various biochemical and mechanical stimuli, fibroblasts undergo a differentiation/transformation into a myofibroblastic phenotype. An intermediate proto-myofibroblast stage has been proposed for some fibroblasts [86], but it is unclear whether cardiac fibroblasts adopt this intermediary cell phenotype. In pathological conditions, when numerous cell types infiltrate the myocardium it is unknown if any of these cells transform directly into myofibroblasts or must they first differentiate into a fibroblast.
Figure 2
Figure 2. New Tools for Identifying Fibroblasts
Fibroblast activation protein (FAP) may provide a new marker for identifying fibroblasts. A) and B) confocal micrographs of tissue sections from remote myocardium and MI stained for FAP (green) and DAPI (blue). Very little FAP staining was detected in the remote region compared to the infarct. C) and D) confocal micrographs of fibroblasts isolated from remote and MI regions stained for FAP (green), α-SMA (red), and DAPI (blue). In the MI cells, FAP was detected on myofibroblasts whereas on cells from remote myocardium FAP was detected on fibroblasts (arrow; α-SMA - cell) and myofibroblasts (α-SMA + cells). E) Western blot of protein extracts from fibroblasts isolated from MI and remote myocardium. Scale bars = 50 μm.
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References

    1. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87:1285–1342. - PubMed
    1. Caulfield JB, Borg TK. The collagen network of the heart. Lab Invest. 1979;40:364–72. - PubMed
    1. Souders CA, Bowers SLK, Baudino TA. Cardiac Fibroblast: The Renaissance Cell. Circ Res. 2009;105:1164–76. - PMC - PubMed
    1. Fan D, Takawale A, Lee J, Kassiri Z. Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenesis Tissue Repair. 2012;5:15. - PMC - PubMed
    1. Eghbali M, Weber KT. Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression. Mol Cell Biochem. 1990;96:1–14. - PubMed

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