Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis

Pagnozzi, Leah A; Butcher, Jonathan T.

doi:10.3389/fcvm.2017.00083

Cited by 20 publications

(14 citation statements)

References 215 publications

(223 reference statements)

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“…Control cultures were handled in parallel except for the mechanical stretching that was omitted (static cultures). Based on previous results from our laboratory [11] and data from the literature (for review, see [27]), the expression of a panel of genes relevant to MMV and mechanobiology was investigated by qRT-PCR.…”

Section: Cyclic Stretch Increases the Expression Of Tgfβ2 αSma And Cmentioning

confidence: 99%

Mechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways

Blomme

Deroanne

Hulin

et al. 2019

Journal of Molecular and Cellular Cardiology

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The mitral valve is a complex multilayered structure populated by fibroblast-like cells, valvular interstitial cells (VIC) which are embedded in an extracellular matrix (ECM) scaffold and are submitted to the mechanical deformations affecting valve at each heartbeat, for an average of 40 million times per year. Myxomatous mitral valve (MMV) is the most frequent heart valve disease characterized by disruption of several valvular structures due to alterations of their ECM preventing the complete closure of the valve resulting in symptoms of prolapse and regurgitation. VIC and their ECM exhibit reciprocal dynamic processes between the mechanical signals issued from the ECM and the modulation of VIC phenotype responsible for ECM homeostasis of the valve. Abnormal perception and responsiveness of VIC to mechanical stress may induce an inappropriate adaptative remodeling of the valve progressively leading to MMV. To investigate the response of human VIC to mechanical strain and identify the molecular mechanisms of mechano-transduction in these cells, a cyclic equibiaxial elongation of 14% at the cardiac frequency of 1.16 Hz was applied to VIC by using a Flexercell-4000 T™ apparatus for increasing time (from 1 h to 8 h). We showed that cyclic stretch induces an early (1 h) and transient over-expression of TGFβ2 and αSMA. CTGF, a profibrotic growth factor promoting the synthesis of ECM components, was strongly induced after 1 and 2 h of stretching and still upregulated at 8 h. The mechanical stress-induced CTGF up-regulation was dependent on RhoC, but not RhoA, as demonstrated by siRNA-mediated silencing approaches, and further supported by evidencing RhoC activation upon cell stretching and suppression of cell response by pharmacological inhibition of the effector ROCK1/2. It was also dependent on the MEK/Erk1/2 pathway which was activated by mechanical stress independently of RhoC and ROCK. Finally, mechanical stretching induced the nuclear translocation of myocardin related transcription factor-A (MRTF-A) which forms a transcriptional complex with SRF to promote the expression of target genes, notably CTGF. Treatment of stretched cultures with inhibitors of the identified pathways (ROCK1/2, MEK/ Erk1/2, MRTF-A translocation) blocked CTGF overexpression and abrogated the increased MRTF-A nuclear translocation. CTGF is up-regulated in many pathological processes involving mechanically challenged organs, promotes ECM accumulation and is considered as a hallmark of fibrotic diseases. Pharmacological targeting of MRTF-A by newly developed inhibitors may represent a relevant therapy for MMV.

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Section: Cyclic Stretch Increases the Expression Of Tgfβ2 αSma And Cmentioning

confidence: 99%

Mechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways

Blomme

Deroanne

Hulin

et al. 2019

Journal of Molecular and Cellular Cardiology

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“…(3) Influencing the tissue microenvironment through mechanosensing subcellular organelle like caveolae [26]-"Cells and their extracellular matrix exhibit a dynamic reciprocity in the growth and formation of tissue through mechanotransduction and continuously adapt to physical cues in their environment through gene, protein, and cytokine expression" [27].…”

Section: Mechanism Of Action For Practice Of Breathingmentioning

confidence: 99%

Breathing Signature as Vitality Score Index Created by Exercises of Qigong: Implications of Artificial Intelligence Tools Used in Traditional Chinese Medicine

Zhang

Loudon

et al. 2019

JFMK

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Rising concerns about the short- and long-term detrimental consequences of administration of conventional pharmacopeia are fueling the search for alternative, complementary, personalized, and comprehensive approaches to human healthcare. Qigong, a form of Traditional Chinese Medicine, represents a viable alternative approach. Here, we started with the practical, philosophical, and psychological background of Ki (in Japanese) or Qi (in Chinese) and their relationship to Qigong theory and clinical application. Noting the drawbacks of the current state of Qigong clinic, herein we propose that to manage the unique aspects of the Eastern ‘non-linearity’ and ‘holistic’ approach, it needs to be integrated with the Western “linearity” “one-direction” approach. This is done through developing the concepts of “Qigong breathing signatures,” which can define our life breathing patterns associated with diseases using machine learning technology. We predict that this can be achieved by establishing an artificial intelligence (AI)-Medicine training camp of databases, which will integrate Qigong-like breathing patterns with different pathologies unique to individuals. Such an integrated connection will allow the AI-Medicine algorithm to identify breathing patterns and guide medical intervention. This unique view of potentially connecting Eastern Medicine and Western Technology can further add a novel insight to our current understanding of both Western and Eastern medicine, thereby establishing a vitality score index (VSI) that can predict the outcomes of lifestyle behaviors and medical conditions.

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“…Mecanotransducción y bioingeniería. La mecanotrasducción es entendida como un evento molecular dinámico, donde las fuerzas mecánicas provenientes del medio, como un aparato de adelantamiento o un cambio de oclusión, se convierten en señales bioquímicas intracelulares debido a que producen una respuesta de adaptación celular en la matriz celular o hasta la misma expresión génica 71,72 . A nivel condilar la evidencia experimental disponible demuestra que el estrés mecánico constante e intermitente infiere en la capacidad de proliferación celular y la síntesis de matriz en el cartílago condilar 39,73 .…”

Section: Factor De Crecimiento Vascular Endotelial (Vegf)unclassified

Crecimiento del cartílago condilar. Una revisión de la literatura

Peláez

Murillo

Parada

2018

Odontol. sanmarquina

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El cóndilo mandibular es un cartílago secundario caracterizado por su respuesta a cargas funcionales y mecánicas. Su estimulación repetida desencadena una serie de eventos que parecen aumentar el número de células mesenquimales de replicación. En esta revisión de la literatura se presentan los hallazgos fundamentales para comprender los factores que condicionan el crecimiento condilar. Se analizaron los siguientes tópicos asociados: embriología, influencia genética y ambiental, función como centro de crecimiento y la bioingeniería aplicada a este campo. Se evidenció en la literatura revisada que el cóndilo actúa como principal centro de crecimiento adaptativo regional y que la regulación del desarrollo está determinada por factores genéticos y epigenéticos que modifican la expresión de factores de transcripción y crecimiento.

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Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis

Cited by 20 publications

References 215 publications

Mechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways

Mechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways

Breathing Signature as Vitality Score Index Created by Exercises of Qigong: Implications of Artificial Intelligence Tools Used in Traditional Chinese Medicine

Crecimiento del cartílago condilar. Una revisión de la literatura

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