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Extracellular Matrix and Fibroblast Communication Following Myocardial Infarction

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Abstract

The extracellular matrix (ECM) provides structural support by serving as a scaffold for cells, and as such the ECM maintains normal tissue homeostasis and mediates the repair response following injury. In response to myocardial infarction (MI), ECM expression is generally upregulated in the left ventricle (LV), which regulates LV remodeling by modulating scar formation. The ECM directly affects scar formation by regulating growth factor release and cell adhesion and indirectly affects scar formation by regulating the inflammatory, angiogenic, and fibroblast responses. This review summarizes the current literature on ECM expression patterns and fibroblast mechanisms in the myocardium, focusing on the ECM response to MI. In addition, we discuss future research areas that are needed to better understand the molecular mechanisms of ECM action, both in general and as a means to optimize infarct healing.

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Acknowledgments

We acknowledge support from NIH-National Center for Complementary and Alternative Medicine for 1K99AT006704-01 to GVH; and from NIH/NHLBI HHSN 268201000036C (N01-HV-00244) for the San Antonio Cardiovascular Proteomics Center and R01 HL075360, the Max and Minnie Tomerlin Voelcker Fund, and the Veteran’s Administration (Merit) to MLL.

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Authors and Affiliations

  1. San Antonio Cardiovascular Proteomics Center, Barshop Institute for Longevity and Aging Studies, Division of Geriatrics, Gerontology and Palliative Medicine, Department of Medicine, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, MC 7755, San Antonio, TX, 78245, USA

    Yonggang Ma, Ganesh V. Halade & Merry L. Lindsey

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  1. Yonggang Ma
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  2. Ganesh V. Halade
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  3. Merry L. Lindsey
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Correspondence to Merry L. Lindsey.

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Statement of Clinical Relevance

Myocardial infarction (MI) is a leading cause in morbidity and mortality worldwide. Although 1-month survival rates have dramatically improved over the past 30 years, the number of patients that progress to congestive heart failure has increased and the 5-year survival rates for heart failure remain approximately 50 %. Additional therapeutic approaches that can delay, limit, or reverse adverse remodeling, therefore, are needed.

Following MI, a reparative scar predominantly containing collagen is formed to replace necrotic myocytes. The balance between extracellular matrix (ECM) synthesis and degradation is critical for stable scar repair. Excessive ECM deposition increases wall stiffness and diastolic dysfunction, while insufficient ECM accumulation and impaired collagen cross-linking contribute to progressive infarct wall thinning and dilation of the left ventricle chamber. In this review, we summarize the current understanding of the roles of different ECM molecules in the MI setting. A better understanding of how individual ECM molecules regulate the post-MI remodeling response is needed, to identify promising intervention targets to stimulate an optimal infarct healing response.

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Ma, Y., Halade, G.V. & Lindsey, M.L. Extracellular Matrix and Fibroblast Communication Following Myocardial Infarction. J. of Cardiovasc. Trans. Res. 5, 848–857 (2012). https://doi.org/10.1007/s12265-012-9398-z

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  • DOI: https://doi.org/10.1007/s12265-012-9398-z

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