The Janus face of myofibroblasts in the remodeling heart

Hermans, Kevin C.M.; Daskalopoulos, Evangelos P.; Blankesteijn, W. Matthijs

doi:10.1016/j.yjmcc.2015.11.017

Cited by 24 publications

(19 citation statements)

References 65 publications

(81 reference statements)

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“…Our group has recently shown that ECM fragments called matrikines (matricryptins) can regulate fibroblast physiology, thus affecting cardiac repair post-MI [69]. It has been shown that myofibroblasts can remain active in the infarct region, even up to 18 years post-MI in humans [70, 71]. Therefore, how long the maturation phase lasts is highly variable at the individual level, and the continual persistence of fibroblasts post-MI is likely required to maintain the new homeostasis.…”

Section: Knowledge Gap 2 Post-mi Cardiac Fibroblast Phenotypes Have mentioning

confidence: 99%

Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps

Iyer

Jung

et al. 2017

Trends in Pharmacological Sciences

157

147

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In response to myocardial infarction (MI), the wound healing response of the left ventricle (LV) consists of overlapping inflammatory, proliferative, and maturation phases; and the cardiac fibroblast is a key cell type involved in each phase. It has recently been appreciated that early post-MI, fibroblasts transform to a pro-inflammatory phenotype and secrete cytokines and chemokines as well as matrix metalloproteinases. Later post-MI, fibroblasts are activated to anti-inflammatory and pro-reparative phenotypes and generate anti-inflammatory and pro-angiogenic factors and extracellular matrix components that form the infarct scar. Additional studies are needed to systematically examine how fibroblast activation shifts over the time frame of MI response and how modulation at different activation stages could alter wound healing and LV remodeling in distinct ways. This review will summarize current fibroblast knowledge as a foundation to discuss existing knowledge gaps.

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Section: Knowledge Gap 2 Post-mi Cardiac Fibroblast Phenotypes Have mentioning

confidence: 99%

Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps

Iyer

Jung

et al. 2017

Trends in Pharmacological Sciences

157

147

View full text Add to dashboard Cite

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“…As such, upregulation of ECM genes and remodeling of the ECM ensures structural stability to withstand increases in mechanical load and repair the myocardium following injury; e.g., fibrosis is necessary to prevent myocardial rupture following an infarction. However, persistently high ECM-producing activity is associated with myocardial stiffening and impaired function [11,48]. …”

Section: Cardiac Fibroblasts and Mechanotransductionmentioning

confidence: 99%

The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart

Herum

Lunde

McCulloch

et al. 2017

JCM

136

123

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Cardiac fibrosis, the excessive accumulation of extracellular matrix (ECM), remains an unresolved problem in most forms of heart disease. In order to be successful in preventing, attenuating or reversing cardiac fibrosis, it is essential to understand the processes leading to ECM production and accumulation. Cardiac fibroblasts are the main producers of cardiac ECM, and harbor great phenotypic plasticity. They are activated by the disease-associated changes in mechanical properties of the heart, including stretch and increased tissue stiffness. Despite much remaining unknown, an interesting body of evidence exists on how mechanical forces are translated into transcriptional responses important for determination of fibroblast phenotype and production of ECM constituents. Such mechanotransduction can occur at multiple cellular locations including the plasma membrane, cytoskeleton and nucleus. Moreover, the ECM functions as a reservoir of pro-fibrotic signaling molecules that can be released upon mechanical stress. We here review the current status of knowledge of mechanotransduction signaling pathways in cardiac fibroblasts that culminate in pro-fibrotic gene expression.

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“…If the molecular secrets of remodelling could be unlocked, more specific interventions to induce full cardiac repair and recovery might result. The scientific literature provides many reviews describing the molecular changes involved in remodelling, with some recently published [7,8,9,10,11,12]. This, however, is not the scope of our article.…”

Section: Introductionmentioning

confidence: 99%