Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

Casals, Gregori; Fernández‐Varo, Guillermo; Melgar-Lesmes, Pedro; Marfà, Santiago; Reichenbach, Vedrana; Morales-Ruíz, Manuel; Jiménez, Wladimiro

doi:10.1159/000354513

Cited by 13 publications

(9 citation statements)

References 48 publications

(53 reference statements)

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“…MMP-9 activity was examined by gelatin zymography as previously reported in AC16 cell cultures after protein concentration using 3000 MW Amicon Ultra centrifugal filters (Millipore) ( Casals et al, 2013 ). 150 μg of protein per lane were subjected to 10% SDS-PAGE electrophoresis (125 V for 90 min) using 0.2% gelatin-containing gels.…”

Section: Methodsmentioning

confidence: 99%

miR-146a targets c-Fos expression in human cardiac cells

Palomer

Capdevila-Busquets

Botteri

et al. 2015

Disease Models &Amp; Mechanisms

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ABSTRACTmiR-146a is a microRNA whose transcript levels are induced in the heart upon activation of NF-κB, a transcription factor induced by pro-inflammatory molecules (such as TNF-α) that is strongly related to the pathogenesis of cardiac disorders. The main goal of this study consisted of studying new roles of miR-146a in cardiac pathological processes caused by the pro-inflammatory cytokine TNF-α. Our results demonstrate that miR-146a transcript levels were sharply increased in cardiac ventricular tissue of transgenic mice with specific overexpression of TNF-α in the heart, and also in a cardiomyocyte cell line of human origin (AC16) exposed to TNF-α. Among all the in silico predicted miR-146a target genes, Fos mRNA and protein levels notably decreased after TNF-α treatment or miR-146a overexpression. These changes correlated with a diminution in the DNA-binding activity of AP-1, the Fos-containing transcription factor complex. Interestingly, AP-1 inhibition was accompanied by a reduction in matrix metalloproteinase (MMP)-9 mRNA levels in human cardiac cells. The specific regulation of this MMP by miR-146a was further confirmed at the secretion and enzymatic activity levels, as well as after anti-miR-mediated miR-146a inhibition. The results reported here demonstrate that Fos is a direct target of miR-146a activity and that downregulation of the Fos–AP-1 pathway by miR-146a has the capacity to inhibit MMP-9 activity. Given that MMP-9 is an AP-1 target gene involved in cardiac remodeling, myocardial dysfunction and progression of heart failure, these findings suggest that miR-146a might be a new and promising therapeutic tool for treating cardiac disorders associated with enhanced inflammation in the heart.

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Section: Methodsmentioning

confidence: 99%

miR-146a targets c-Fos expression in human cardiac cells

Palomer

Capdevila-Busquets

Botteri

et al. 2015

Disease Models &Amp; Mechanisms

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“…Changes in the matrix may be then conducted to adjacent cells and affect their activity and behavior. For example, the cardiovascular ECM mediates blood flow-induced mechanotransduction [ 2 , 3 ] and adaptive responses of vascular cells and cardiomyocytes to various stress stimuli [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Thrombospondins: A Role in Cardiovascular Disease

Chistiakov

Melnichenko

Myasoedova

et al. 2017

IJMS

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Thrombospondins (TSPs) represent extracellular matrix (ECM) proteins belonging to the TSP family that comprises five members. All TSPs have a complex multidomain structure that permits the interaction with various partners including other ECM proteins, cytokines, receptors, growth factors, etc. Among TSPs, TSP1, TSP2, and TSP4 are the most studied and functionally tested. TSP1 possesses anti-angiogenic activity and is able to activate transforming growth factor (TGF)-β, a potent profibrotic and anti-inflammatory factor. Both TSP2 and TSP4 are implicated in the control of ECM composition in hypertrophic hearts. TSP1, TSP2, and TSP4 also influence cardiac remodeling by affecting collagen production, activity of matrix metalloproteinases and TGF-β signaling, myofibroblast differentiation, cardiomyocyte apoptosis, and stretch-mediated enhancement of myocardial contraction. The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of TSPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis. Targeting of TSPs has a significant therapeutic value for treatment of cardiovascular disease. The activation of cardiac TSP signaling in stress and pressure overload may be therefore beneficial.

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“…The development of new antihypertensive and antiremodeling drugs, which are expected to decrease the morbidity and mortality of hypertension, is the focus of this research. Endothelial dysfunction is plays an important role in both the pathogenesis and the progression of hypertensive heart disease [1][2][3]. The pathophysiological mechanisms of endothelial dysfunction are related to a decrease in the bioavailability of NO, as well as decreased PGI 2 content and augmented ET-1 synthesis, release, and activity [4].…”

Section: Introductionmentioning

confidence: 99%

The Effects of 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone on Pressure Overload-Induced Cardiac Remodeling in Rats and the Endothelial Mechanisms Based on PGI2

Huang

Tang

Liang

et al. 2015

Cell Physiol Biochem

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Aim: The primary objective of this study was to study the effects of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on pressure overload-induced cardiac remodeling in rats, as well as the endothelial mechanisms based on PGI₂. Methods: Six weeks following surgery, rats were divided randomly into the following groups: a sham group, a model group, an MHBFC 12 mg/kg/day group (MHBFC 12), an indomethacin 2 mg/kg/day group (Indo 2), and an Indo 2+ MHBFC 12 group. The MS 4000 organism signal system was used to record the rats' hemodynamic indices. Additionally, the heart weight was determined, and the cardiac remodeling index was calculated. HE and Masson's stains were utilized to perform histological analyses; the immunofluorescence was used to observe the microvessel density of myocardial tissue; the colorimetric method was used to determine the hydroxyproline content of cardiac tissue; the ELISA method was used to measure the plasma PGI₂ content; and transmission electron microscopy was used to observe the ultrastructure of the myocardium. Results: A hyperdynamic circulation state, cardiac remodeling, decreased microvessel density and decreased plasma PGI₂ content were each observed in the model group compared with the sham group, in which any changes in the above parameters were effectively reversed by MHBFC. Single-use Indo administration resulted in the progression of these pathophysiological changes; however, MHBFC prevented the worsening of these parameters. Conclusion: MHBFC significantly reverses pressure overload-induced cardiac remodeling, and its mechanism may partially contribute to the amelioration of endothelial cell function and the augmentation of PGI₂ synthesis and secretion.

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Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

Cited by 13 publications

References 48 publications

miR-146a targets c-Fos expression in human cardiac cells

miR-146a targets c-Fos expression in human cardiac cells

Thrombospondins: A Role in Cardiovascular Disease

The Effects of 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone on Pressure Overload-Induced Cardiac Remodeling in Rats and the Endothelial Mechanisms Based on PGI2

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