Multiaxial Myocardial Mechanics and Extracellular Matrix Remodeling: Mechanochemical Regulation of Cardiac Fibroblast Function

Lee, Ann A.; McCulloch, Andrew D.

doi:10.1007/978-1-4615-5959-7_19

Cited by 8 publications

(5 citation statements)

References 49 publications

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“…(Sadoshima et al, 1992; Carver et al, 1991; Vanderploeg, 2004). Furthermore, the peak strains and frequency used in our experiments are similar to those experienced by cells within the cardiac wall (~10% strain in magnitude) (Lee and McCulloch, 1997; Gupta and Grande-Allen, 2006); therefore it is possible for mast cells to encounter these loading strains and frequency in vivo. By extending these studies to include tissue-specific loading regimens (e.g., alternative frequencies and duty cycles), multiple ECM components (such as collagen), and partner cell types (e.g., fibroblasts or myocytes), we will gain substantial insight into the microenvironmental cues that regulate mast cell degranulation.…”

Section: Discussionmentioning

confidence: 70%

Mechanical loading promotes mast cell degranulation via RGD-integrin dependent pathways

Fowlkes

Wilson

Carver

et al. 2013

Journal of Biomechanics

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Mast cells are known to respond to a number of stimuli, such as IgE antibody–antigen complexes, pathogens, chemical compounds, and physical stimulation, resulting in the activation of these cells and subsequent release of cytokines, inflammatory mediators and granules which can influence the pathophysiology of neighboring cells. Although different forms of physical stimulation (i.e. shear stress and acupuncture) have been investigated, the effect of cyclic tensile loading on mast cell activation has not. To characterize the response of mast cells to tensile loading, RBL-2H3 cells were embedded in a 3-dimensional fibrin construct and subjected to 24 h of cyclic loading at 0%, 5% or 10% peak tensile strain. Mechanical loading significantly increased RBL-2H3 cell secretion of β-hexosaminidase (2.1- to 2.3-fold, respectively) in a load- and time-dependent manner when compared to the controls. Furthermore, no evidence of load-induced cell death or alterations in cell proliferation was observed. To determine if RGD-dependent integrins mediated the degranulation of mast cells during mechanical loading, cell–matrix interactions were inhibited by treating the cells with echistatin, a disintegrin that binds RGD-dependent integrins. Treatment with echistatin significantly attenuated load-induced degranulation without compromising cell viability. These results suggest a novel mechanism through which mechanical loading induces mast cell activation via RGD binding integrins.

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Section: Discussionmentioning

confidence: 70%

Mechanical loading promotes mast cell degranulation via RGD-integrin dependent pathways

Fowlkes

Wilson

Carver

et al. 2013

Journal of Biomechanics

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“…This was approximated to be the change in stress over each of the strain ranges. Myocardial physiological strain has been reported to range from 0.10 to 0.15; 7,11,16,21 to account for the lower and higher ends, a mechanical assessment was performed between 0.05 and 0.10 and between 0.10 and 0.15 Green-Lagrange strain, where 0.05-0.10 corresponded to the linear toe region in stress-strain curves (Figure 6A and 6B). A strain range of 0.15-0.20 (Figure 6A and 6B), which generally corresponded to the second linear portion in stress-strain curves, was analyzed as an extreme case that could potentially represent a hypertrophied borderzone.…”

Section: Resultsmentioning

confidence: 99%

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

et al. 2013

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The material properties of myocardium are an important determinant of global left ventricular function. Myocardial infarction results in a series of maladaptive geometric alterations which lead to increased stress and risk of heart failure. In vivo studies have demonstrated that material injection can mitigate these changes. More importantly, the material properties of these injectates can be tuned to minimize wall thinning and ventricular dilation. The current investigation combines experimental data and finite element modeling to correlate how injectate mechanics and volume influence myocardial wall stress. Experimentally, mechanics were characterized with biaxial testing and injected hydrogel volumes were measured with magnetic resonance imaging. Injection of hyaluronic acid hydrogel increased the stiffness of the myocardium/hydrogel composite region in an anisotropic manner, significantly increasing the modulus in the longitudinal direction compared to control myocardium. Increased stiffness, in combination with increased volume from hydrogel injection, reduced the global average fiber stress by ~14% and the transmural average by ~26% in the simulations. Additionally, stiffening in an anisotropic manner enhanced the influence of hydrogel treatment in decreasing stress. Overall, this work provides insight on how injectable biomaterials can be used to attenuate wall stress and provides tools to further optimize material properties for therapeutic applications.

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“…Moreover, cytokine activation and signaling such as that for tumor necrosis factor-␣ (TNF) is highly compartmentalized within the myocardial interstitium (95,111). Growth factors such as transforming growth factor-␤ (TGF) are stored in a latent form within the myocardial interstitium and thereby form a reservoir of signaling molecules that directly influence myocardial ECM synthesis and degradation (67,82,218,298,399,443). Moreover, mechanical stimuli such as stress or strain are likely transduced through the myocardial ECM to the cardiac myocyte, which in turn would directly affect myocyte growth (35, 37, 69, 217, 249 -251, 313, 547).…”

Section: A Structure and Function Of The Myocardial Matrixmentioning

confidence: 99%

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

1,007

1,023

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It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

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Multiaxial Myocardial Mechanics and Extracellular Matrix Remodeling: Mechanochemical Regulation of Cardiac Fibroblast Function

Cited by 8 publications

References 49 publications

Mechanical loading promotes mast cell degranulation via RGD-integrin dependent pathways

Mechanical loading promotes mast cell degranulation via RGD-integrin dependent pathways

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

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