Differential integrin expression by cardiac fibroblasts from hypertensive and exercise-trained rat hearts

Burgess, Maria Lonnett; Terracio, Louis; Hirozane, Toshiro; Borg, Thomas K.

doi:10.1016/s1054-8807(01)00104-1

Cited by 66 publications

(47 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another fibronectin-binding integrin, α8β1, is specifically enhanced in MyoFBs within fibrotic hearts (Bouzeghrane et al, 2004). Overall, β1 integrin expression is increased in fibrotic and hypertrophic hearts and, moreover, fibroblast-specific deletion of β1 integrin causes insufficient wound healing and reduced MyoFB differentiation in a dermal model (Burgess et al, 2002;Liu and Leask, 2013;Liu et al, 2010). Taken together, these data suggest that, despite their protective effect on CMs, β1 integrins exert a profibrotic effect in heart fibroblasts during disease.…”

Section: Mechanosensors Of Stressmentioning

confidence: 79%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

117

View full text Add to dashboard Cite

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.

show abstract

Section: Mechanosensors Of Stressmentioning

confidence: 79%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

117

View full text Add to dashboard Cite

show abstract

“…Since the ECM is integrated to the intracellular compartment through a series of transmembrane proteins, the integrins, it is likely that changes in mechanical stress placed on the myocardium would alter intracellular signaling pathways involved in MMP transcriptional activity (51,249,356,366,373,396,448). Increased transmural pressure increased relative MMP-2 and MMP-9 levels using an ex vivo arterial preparation (70).…”

Section: Mechanical Stimuli and Mmp Transcriptionmentioning

confidence: 99%

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

Spinale¹

2007

Physiological Reviews

1,006

1,023

View full text Add to dashboard Cite

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.

show abstract

“…These cells were maintained in DMEM containing 10% neonatal bovine serum and 5% fetal calf serum, with medium replacement every other day, and used before passage number 3. 15 One million fibroblasts were allowed to adhere in DMEM with 10% neonatal bovine serum and 5% fetal calf serum for 24 hours before rinsing with Mosconas salt solution and serum starvation for 24 hours in DMEM-F12. Medium was then replaced with DMEM with 1.5% FBS containing 100, 500, or 1000 mU/mL of skin recombinant tryptase (Promega) for 24, 48, or 72 hours.…”

Section: Cardiac Fibroblast Collagen Synthesis and Proliferationmentioning

confidence: 99%

Cardiac Mast Cells Mediate Left Ventricular Fibrosis in the Hypertensive Rat Heart

et al. 2009

View full text Add to dashboard Cite

Abstract-Correlative data suggest that cardiac mast cells are a component of the inflammatory response that is important to hypertension-induced adverse myocardial remodeling. However, a causal relationship has not been established. We hypothesized that adverse myocardial remodeling would be inhibited by preventing the release of mast cell products that may interact with fibroblasts and other inflammatory cells. Eight-week-old male spontaneously hypertensive rats were treated for 12 weeks with the mast cell stabilizing compound nedocromil (30 mg/kg per day). Age-matched Wistar-Kyoto rats served as controls. Nedocromil prevented left ventricular fibrosis in the spontaneously hypertensive rat independent of hypertrophy and blood pressure, despite cardiac mast cell density being elevated. The mast cell protease tryptase was elevated in the spontaneously hypertensive rat myocardium and was normalized by nedocromil. Treatment of isolated adult spontaneously hypertensive rat cardiac fibroblasts with tryptase induced collagen synthesis and proliferation, suggesting this as a possible mechanism of mast cell-mediated fibrosis. In addition, nedocromil prevented macrophage infiltration into the ventricle. The inflammatory cytokines interferon-␥ and interleukin (IL)-4 were increased in the spontaneously hypertensive rat and normalized by nedocromil, whereas IL-6 and IL-10 were decreased in the spontaneously hypertensive rat, with nedocromil treatment normalizing IL-6 and increasing IL-10 above the control. These results demonstrate for the first time a causal relationship between mast cell activation and fibrosis in the hypertensive heart. Furthermore, these results identify several mechanisms, including tryptase, inflammatory cell recruitment, and cytokine regulation, by which mast cells may mediate hypertension-induced left ventricular fibrosis.

show abstract

Differential integrin expression by cardiac fibroblasts from hypertensive and exercise-trained rat hearts

Cited by 66 publications

References 54 publications

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

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

Cardiac Mast Cells Mediate Left Ventricular Fibrosis in the Hypertensive Rat Heart

Contact Info

Product

Resources

About