Extracellular Matrix Secretion by Cardiac Fibroblasts

Abonnenc, Mélanie; Nabeebaccus, Adam; Mayr, Ursula; Barallobre-Barreiro, Javier; Dong, Xuebin; Cuello, Friederike; Sur, Sumon; Drozdov, Ignat; Langley, Sarah R.; Lu, Ruifang; Σταθοπούλου, Κωνσταντίνα; Didangelos, Athanasios; Yin, Xiaoke; Zimmermann, Wolfram H.; Shah, Ajay M.; Zampetaki, Anna; Mayr, Manuel

doi:10.1161/circresaha.113.302400

Cited by 157 publications

(150 citation statements)

References 43 publications

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“…In patients, miR-30 levels in the bloodstream are positively associated with left ventricular wall thickness. Intriguingly, miRs can be secreted from cells as vesicular bodies that arise from the plasma membrane or can be simply extruded by cells through membrane shedding (17). Once miRs are packed into specific multivesicular bodies, they can undergo unidirectional transfer as part of cell-cell communication strategies, establishing an intercellular trafficking network that exchanges genetic information and elicits a variety of phenotypic changes (18).…”

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confidence: 99%

Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

Indolfi¹,

Curcio²

2014

J. Clin. Invest.

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Left ventricular hypertrophy and microRNAsLeft ventricular hypertrophy (LVH) can be elicited by several clinical conditions, including systemic hypertension, cardiac valve disease, and myocardial infarction, that increase cardiac workload. This adaptation is one facet of cardiac remodeling and subsequent heart failure (HF), which is a major cause of death in Western countries (1). In 1970, the Framingham Heart Study revealed that the presence of LVH alone is associated with increased mortality (1). Moreover, recent appraisals of this cohort have also linked LVH to arrhythmic sudden cardiac death (2). Interestingly, inhibition of LVH after transverse aortic constriction prevents HF and increases survival in genetically modified animals (3, 4).Because of the strong correlation between LVH and sudden cardiac death, the mechanisms underlying LVH etiology, and degeneration toward HF, have been studied extensively (4, 5). Several aspects of LVH-dependent HF still need to be clarified, and, in this regard, microRNAs (miRs) could provide additional insights into the mechanisms involved in LVH and HF. miRs are short (17-25 nucleotides) Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, was identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes. These advanced comprehensive analyses represent a major step forward in our understanding of cardiovascular physiopathology, providing a promising adjunctive target for possible therapeutic approaches, namely the miRmediated paracrine signaling network.

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confidence: 99%

Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

Indolfi¹,

Curcio²

2014

J. Clin. Invest.

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“…MiR‐30c has also been shown to negatively regulate cancer metastasis by directly targeting metastasis‐associated genes 54, 55. Several other studies have indicated that miR‐30c is significantly reduced in a model of pathological left ventricular hypertrophy 7, 8. MiR‐30c regulates the production of ECM in TGF‐β‐dependent liver fibrosis 9, 56.…”

Section: Discussionmentioning

confidence: 99%

“…MiRNAs participate in the pathogenesis of different pathological events, including cardiac fibrosis 5. Several members of the miR‐30 family are highly expressed in the brain, with the exception of miR‐30c, which is abundant in cardiac fibroblasts (CFs) and is involved in ventricular fibrosis 6, 7. Several studies have demonstrated that miR‐30c inhibits ventricular collagen synthesis in pathological left ventricular hypertrophy 7, 8.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

Wang

Chen

et al. 2018

J Cellular Molecular Medi

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Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA‐30c (miR‐30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR‐30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR‐30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR‐30c is significantly down‐regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor‐β1 (TGF‐β1). Overexpression of miR‐30c in cardiac fibroblasts (CFs) markedly inhibits CF proliferation, differentiation, migration and collagen production, whereas decrease in miR‐30c leads to the opposite results. Moreover, we identified TGFβRII as a target of miR‐30c. Finally, transferring adeno‐associated virus 9 (AAV9)‐miR‐30c into the inferior vena cava of rats attenuated fibrosis in the left atrium following AAC. These data indicate that miR‐30c attenuates atrial fibrosis via inhibition of CF proliferation, differentiation, migration and collagen production by targeting TGFβRII, suggesting that miR‐30c might be a novel potential therapeutic target for preventing atrial fibrosis.

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“…29 It has been shown that activation of TGF-b-Smad signaling induces the expression of specific miRNAs that, in turn, may modulate TGF-b-Smad signaling in a feedback manor. [30][31][32] For example, TGF-b1 induces miR-9-5p expression, while overexpression of miR-9-5p in lung fibroblasts inhibits TGFbRII expression and prevents myofibroblast differentiation, ECM deposition, and organ fibrogenesis. 31 Here, we found that TGF-b1 induces a decrease in miR-18a-5p.…”

Section: Discussionmentioning

confidence: 99%