Cyclic strain inhibits acute pro-inflammatory gene expression in aortic valve interstitial cells

Smith, Kathryn E.; Metzler, Scott; Warnock, James N.

doi:10.1007/s10237-009-0165-2

Cited by 35 publications

(32 citation statements)

References 21 publications

(23 reference statements)

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“…High local strains can also signal transition from inflammation to fibrosis. In response to increased cyclic strain, aortic VICs (AVICs) express reduced levels of inflammatory markers and increased levels of profibrotic factors including TGF-β1 (Smith et al, 2010). Strain and TGF-β1 together enhance MyoFB differentiation and cell contractility, and increase the formation of calcified nodules by AVICs in dynamic culture Merryman et al, 2007;Santiago et al, 2010).…”

Section: Cardiac Cell Responses To Mechanical Stressmentioning

confidence: 99%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

112

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Fibrotic cardiac disease, a leading cause of death worldwide, manifests as substantial loss of function following maladaptive tissue remodeling. Fibrosis can affect both the heart valves and the myocardium and is characterized by the activation of fibroblasts and accumulation of extracellular matrix. Valvular interstitial cells and cardiac fibroblasts, the cell types responsible for maintenance of cardiac extracellular matrix, are sensitive to changing mechanical environments, and their ability to sense and respond to mechanical forces determines both normal development and the progression of disease. Recent studies have uncovered specific adhesion proteins and mechano-sensitive signaling pathways that contribute to the progression of fibrosis. Integrins form adhesions with the extracellular matrix, and respond to changes in substrate stiffness and extracellular matrix composition. Cadherins mechanically link neighboring cells and are likely to contribute to fibrotic disease propagation. Finally, transition to the active myofibroblast phenotype leads to maladaptive tissue remodeling and enhanced mechanotransductive signaling, forming a positive feedback loop that contributes to heart failure. This Commentary summarizes recent findings on the role of mechanotransduction through integrins and cadherins to perpetuate mechanically induced differentiation and fibrosis in the context of cardiac disease.

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Section: Cardiac Cell Responses To Mechanical Stressmentioning

confidence: 99%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

112

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“…Previous studies have shown that acute changes in gene and protein expression can occur within two hours 16,17 . However, this duration may not be sufficient to study transient gene/protein expression or changes in cellular phenotype as a result of mechanical stress.…”

Section: Discussionmentioning

confidence: 99%

Design of a Cyclic Pressure Bioreactor for the <em>Ex Vivo</em> Study of Aortic Heart Valves

Schipke

Warnock

2011

JoVE

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The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage(1-3). Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease(4). The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve(5). Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors have also been developed to study a range of tissues including cartilage(10), bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the system at the appropriate rate. The system mimicked the dynamic transvalvular pressure levels associated with the aortic valve; a saw tooth wave produced a gradual increase in pressure, typical of the transvalvular pressure gradient that is present across the valve during diastole, followed by a sharp pressure drop depicting valve opening in systole. The LabVIEW program allowed users to control the magnitude and frequency of cyclic pressure. The system was able to subject tissue samples to physiological and pathological pressure conditions. This device can be used to increase our understanding of how heart valves respond to changes in the local mechanical environment.

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“…Using triads of VIC nuclei as fiducials, local strains calculated at a uniaxially applied tissue-level strain of 30% only reached~10% and~20% under circumferential and radial stretches, respectively. Nevertheless, while studies have begun to address the influence of mechanical stretch on in vitro cultured VICs [24,26,[52][53][54][55] and explanted leaflet tissues [19,20], comparatively few studies have investigated the micromechanical interactions between the VICs and ECM in situ [13,56], in order to quantify regional stress distributions associated with the heterogeneous ECM or the stress-strain state of an individual VIC.…”

Section: Discussionmentioning

confidence: 99%

Prediction of matrix-to-cell stress transfer in heart valve tissues

Huang

2014

J Biol Phys

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Non-linear and anisotropic heart valve leaflet tissue mechanics manifest principally from the stratification, orientation, and inhomogeneity of their collagenous microstructures. Disturbance of the native collagen fiber network has clear consequences for valve and leaflet tissue mechanics and presumably, by virtue of their intimate embedment, on the valvular interstitial cell stress-strain state and concomitant phenotype. In the current study, a set of virtual biaxial stretch experiments were conducted on porcine pulmonary valve leaflet tissue photomicrographs via an image-based finite element approach. Stress distribution evolution during diastolic valve closure was predicted at both the tissue and cellular levels. Orthotropic material properties consistent with distinct stages of diastolic loading were applied. Virtual experiments predicted tissue-and cellular-level stress fields, providing insight into how matrix-to-cell stress transfer may be influenced by the inhomogeneous collagen fiber architecture, tissue anisotropic material properties, and the cellular distribution within the leaflet tissue. To the best of the authors' knowledge, this is the first study reporting on the evolution of stress fields at both the tissue and cellular levels in valvular tissue and thus contributes toward refining our collective understanding of valvular tissue micromechanics while providing a computational tool enabling the further study of valvular cell-matrix interactions.

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Cyclic strain inhibits acute pro-inflammatory gene expression in aortic valve interstitial cells

Cited by 35 publications

References 21 publications

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Design of a Cyclic Pressure Bioreactor for the <em>Ex Vivo</em> Study of Aortic Heart Valves

Prediction of matrix-to-cell stress transfer in heart valve tissues

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