Integrin-mediated collagen gel contraction by cardiac fibroblasts. Effects of angiotensin II.

Burgess, Maria Lonnett; Carver, Wayne; Terracio, Louis; Wilson, Steven P.; Wilson, Marlene A.; Borg, Thomas K.

doi:10.1161/01.res.74.2.291

Cited by 104 publications

(66 citation statements)

References 30 publications

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“…The contraction of ECM by cardiac myofibroblasts is an important process in wound healing, and can be studied in vitro by culturing cells in 3D collagen gels. Both Ang II and TGF enhance in vitro collagen gel contraction by CF (Burgess et al, 1994;Drobic et al, 2007;Lijnen et al, 2003).…”

Section: Effect Of Profibrotic Stimuli On Cfmentioning

confidence: 98%

The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction

Nieuwenhoven

Turner

2013

Vascular Pharmacology

123

108

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Cardiac fibroblasts (CF) play a pivotal role in the repair and remodeling of the heart that occurs following myocardial infarction (MI). The transition through the inflammatory, granulation and maturation phases of infarct healing is driven by cellular responses to local levels of cytokines, chemokines and growth factors that fluctuate in a temporal and spatial manner. In the acute inflammatory phase early after MI, CF contribute to the inflammatory milieu through increased secretion of proinflammatory cytokines and chemokines, and they promote extracellular matrix (ECM) degradation by increasing matrix metalloproteinase (MMP) expression and activity. In the granulation phase, CF migrate into the infarct zone, proliferate and produce MMPs and pro-angiogenic molecules to facilitate revascularization.Fibroblasts also undergo a phenotypic change to become myofibroblasts. In the maturation phase, inflammation is reduced by anti-inflammatory cytokines, and increased levels of profibrotic stimuli induce myofibroblasts to synthesize new ECM to form a scar. The scar is contracted through the mechanical force generated by myofibroblasts, preventing cardiac dilation. In this review we discuss the transition from myocardial inflammation to fibrosis with particular focus on how CF respond to alterations in proinflammatory and profibrotic signals. By furthering our understanding of these events, it is hoped that new therapeutic interventions will be developed that selectively reduce adverse myocardial remodeling post-MI, whilst sparing essential repair mechanisms.

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Section: Effect Of Profibrotic Stimuli On Cfmentioning

confidence: 98%

The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction

Nieuwenhoven

Turner

2013

Vascular Pharmacology

123

108

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“…To begin to address this issue and the minimize confounding influences that could be encountered in vivo, primary cultures of myocardial fibroblasts were incubated in the presence and absence of TNF-␣ blocking antibody. Primary cultures of myocardial porcine fibroblasts were established using well-described techniques (2,27). Briefly, LV midmyocardial samples (1 ϫ 2 mm) were harvested from anesthetized pigs (25 kg, n ϭ 3, Yorkshire; Hambone Farms, SC) using sterile techniques and plated onto flasks (75 cm 2 , Falcon, Becton-Dickinson; Franklin Lakes, NJ) containing standard cell culture media (DMEM, GIBCO-BRL/Invitrogen; Grand Island, NY) supplemented with 10% fetal bovine serum.…”

Section: Myocardial Fibroblast Incubation With Tnf-␣ Blocking Antibodymentioning

confidence: 99%

“…These primary cultures were used during cell passages 2-4 and were subsequently grown to an 80% confluent monolayer in 25-cm 2 flasks (Falcon). These cultures were confirmed to be fibroblasts due to the spindle-shaped morphology and a complete absence of staining for smooth muscle actin (2,4). For these experiments, identically matched fibroblast cultures were incubated in serum-free media in the absence or presence of TNF-␣ blocking protein (2,000 ng/ml, huTNFR: Fc, Immunex) for 24 h. The conditioned cell media were then collected and immediately frozen for MMP zymographic analysis.…”

Section: Myocardial Fibroblast Incubation With Tnf-␣ Blocking Antibodymentioning

confidence: 99%

TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

Bradham

Moe

Wendt

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

113

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. TNF-␣ and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling. Am J Physiol Heart Circ Physiol 282: H1288-H1295, 2002; 10.1152/ajpheart.00526. 2001.-The cytokine tumor necrosis factor (TNF)-␣ has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. Matrix metalloproteinases (MMPs) have been implicated in cardiac remodeling and can be regulated by TNF-␣. This study tested the central hypothesis that administration of a TNF-␣ blocking protein would prevent the induction of MMPs and alter the course of myocardial remodeling in developing LV failure. Adult dogs were randomly assigned to the following groups: 1) chronic pacing (250 beats/min, 28 days, n ϭ 12), 2) chronic pacing with concomitant administration of a TNF-␣ blocking protein (TNF block) using a soluble p75 TNF receptor fusion protein (TNFR:Fc; administered at 0.5 mg/kg twice a week subcutaneously, n ϭ 7), and 3) normal controls (n ϭ 10). LV end-diastolic volume increased from control with chronic pacing (83 Ϯ 12 vs. 118 Ϯ 10 ml, P Ͻ 0.05) and was reduced with TNF block (97 Ϯ 9 ml, P Ͻ 0.05). MMP zymographic levels (92 kDa, pixels) increased from control with chronic pacing (36,848 Ϯ 9,593 vs. 87,247 Ϯ 12,912, P Ͻ 0.05) and was normalized by TNF block. Myocardial MMP-9 and MMP-13 levels by immunoblot increased with chronic pacing relative to controls (130 Ϯ 10% and 118 Ϯ 6%, P Ͻ 0.05) and was normalized by TNF block. These results provide evidence to suggest that TNF-␣ contributes to the myocardial remodeling process in evolving heart failure through the local induction of specific MMPs.tumor necrosis factor-␣; chronic pacing A MILESTONE IN THE DEVELOPMENT of left ventricular (LV) failure is myocardial remodeling. Myocardial remodeling can be defined as structural changes in the cellular and extracellular matrix resulting in compositional changes within the LV wall. An acceleration of the LV remodeling process is associated with greater morbidity and mortality in patients with LV failure (3, 16). While a number of biological systems influence myocardial matrix structure and function, a family of proteases called matrix metalloproteinases (MMPs) likely contributes to the remodeling process (4, 8, 12-15, 18, 26, 29-31). MMP activity is regulated at several levels, including transcription and posttranslational modification (8, 21). MMP activity can be inhibited by an endogenous class of proteins called the tissue inhibitors of MMPs (TIMPs). A number of biologically active molecules can induce MMP expression, including the pleotrophic cytokine tumor necrosis factor (TNF)-␣, which has been demonstrated to increase MMPs in vitro (10, 25). Increased TNF-␣ levels have been previously associated with LV myocardial remodeling (1, 17). TNF-␣ is synthesized as a membrane-bound protein and subsequently processed and cleaved to a soluble form that circulates as a stable homotrimer (5). TNF-␣ binding to cell surface receptors results in the activation of intracellular signaling ...

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“…Studies with isolated CF show that TGFβ1 induces differentiation of CF to CMF (Swaney et al, 2005), and stimulates collagen production (Butt et al, 1995;Chua et al, 1991;Eghbali et al, 1991;Lijnen et al, 2000;Swaney et al, 2005). In addition, TGFβ1 enhances in vitro collagen gel contraction by CF (Burgess et al, 1994;Drobic et al, 2007;Lijnen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Combined effects of interleukin-1α and transforming growth factor-β1 on modulation of human cardiac fibroblast function

et al. 2013

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A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractDuring cardiac remodeling, cardiac fibroblasts (CF) are influenced by increased levels of interleukin-1α (IL-1α) and transforming growth factor-β1 (TGFβ1). The present study investigated the interaction between these two important cytokines on function of human CF and their differentiation to myofibroblasts (CMF). CF were isolated from human atrial appendage and exposed to IL-1α and/or TGFβ1 (both 0.1 ng/ml). mRNA expression levels of selected genes were determined after 6-24 h by real-time RT-PCR, while protein levels were analyzed at 24-48 h by ELISA or Western blot.Activation of canonical signaling pathways (NFB, Smad3, p38 MAPK) was determined by Western blotting. Differentiation to CMF was examined by collagen gel contraction assays. Exposure of CF to IL-1α alone enhanced levels of IL-6, IL-8, matrix metalloproteinase-3 (MMP3) and collagen III (COL3A1), but reduced the CMF markers α-smooth muscle actin (αSMA) and connective tissue growth factor (CTGF/CCN2). By contrast, TGFβ1 alone had minor effects on IL-6, IL-8 and MMP3levels, but significantly increased levels of the CMF markers αSMA, CTGF, COL1A1 and COL3A1.Co-stimulation with both IL-1α and TGFβ1 increased MMP3 expression synergistically. Furthermore, while TGFβ1 had no effect on IL-1α-induced IL-6 or IL-8 levels, co-stimulation inhibited the TGFβ1-induced increase in αSMA and blocked the gel contraction caused by TGFβ1. Combining IL-1α and TGFβ1 had no apparent effect on their canonical signaling pathways. In conclusion, IL-1α and TGFβ1 act synergistically to stimulate MMP3 expression in CF. Moreover, IL-1α has a dominant inhibitory effect on the phenotypic switch of CF to CMF induced by TGFβ1.

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Integrin-mediated collagen gel contraction by cardiac fibroblasts. Effects of angiotensin II.

Cited by 104 publications

References 30 publications

The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction

The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction

TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

Combined effects of interleukin-1α and transforming growth factor-β1 on modulation of human cardiac fibroblast function

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