Differential Responses of Adult Cardiac Fibroblasts to in vitro Biaxial Strain Patterns

Lee, Ann A.; Delhaas, Tammo; McCulloch, Andrew D.; Villarreal, Francisco

doi:10.1006/jmcc.1999.1017

Cited by 139 publications

(113 citation statements)

References 29 publications

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“…Previously, this issue has not been specifically assessed. However, our findings are consistent with recent reports of gene and signaling protein activation 30 and upregulation of fibronectin gene expression 31 by short applications of static tensile strain to isolated rat CFs.…”

Section: Discussionsupporting

confidence: 93%

Myocardial Fibrosis in Chronic Aortic Regurgitation

et al. 2002

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Background — Myocardial fibrosis is common in patients with chronic aortic regurgitation (AR). Experimentally, fibrosis with disproportionate noncollagen extracellular matrix (ECM) elements precedes and contributes to heart failure in AR. Method and Results — We assessed [ 3 H]-glucosamine and [ 3 H]-proline incorporation in ECM, variations in cardiac fibroblast (CF) gene expression, and synthesis of specific ECM proteins in CF cultured from rabbits with surgically induced chronic AR versus controls. To determine whether these variations are primary responses to AR, normal CF were exposed to mechanical strain that mimicked that of AR. Compared with normal CF, AR CF incorporated more glucosamine (1.8:1, P =0.001) into ECM, showed fibronectin gene upregulation (2.0:1, P =0.02), and synthesized more fibronectin (2:1 by Western blot, P <0.06; 1.5:1 by affinity chromatography, P =0.02). Proline incorporation was unchanged by AR (1.1:1, NS); collagen synthesis was unaffected (type I, 0.9:1; type III, 1.0:1, NS). Normal CF exposed to cyclical mechanical strain during culture showed parallel results: glucosamine incorporation increased with strain (2.1:1, P <0.001), proline incorporation was unaffected (1.1:1, NS), fibronectin gene expression (1.6:1, P =0.07) and fibronectin synthesis (Western analysis, 1.3:1, P <0.01; chromatography, 1.9:1, NS) were upregulated. Conclusions — In AR, CF produce abnormal proportions of noncollagen ECM, specifically fibronectin, with relatively little change in collagen synthesis. At least in part, this is a primary response to strain imposed on CF by AR. Further study must relate these findings to the pathogenesis of heart failure in AR.

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Section: Discussionsupporting

confidence: 93%

Myocardial Fibrosis in Chronic Aortic Regurgitation

et al. 2002

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“…These studies have used cardiac fibroblasts on 2D substrata and have shown an increase in collagen production in response to both static and cyclic stretch (3,20,26). We have found that cardiac fibroblasts in 3DTC convert to myofibroblasts through interaction with the scaffold and that stretch induces phenotypic conversion to fibroblasts with a concomitant reduction in collagen production.…”

Section: Discussionmentioning

confidence: 90%

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Poobalarahi¹,

Baicu²,

Bradshaw³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Myofibroblasts are a differentiated fibroblast cell type characterized by increased contractile capacity and elevated production of extracellular matrix (ECM) proteins. In the heart, myofibroblast expression is implicated in fibrosis associated with pressure-overload hypertrophy, among other pathologies. Although enhanced expression of ECM proteins by myofibroblasts is established, few studies have addressed the nature of the ECM deposited by myofibroblasts. To characterize ECM production and assembly by cardiac myofibroblasts, we developed a threedimensional (3D) culture system using primary cardiac fibroblasts seeded into a nylon mesh that allows us to reversibly interconvert between myofibroblast and fibroblast phenotypes. We report that an increase in collagen I production by myofibroblasts was accompanied by a significant increase in collagen deposition into insoluble ECM. Furthermore, myofibroblasts exhibited increased levels of procollagen ␣1(I) with C-propeptide attached (and N-propeptide removed) relative to procollagen ␣1(I) compared with fibroblast cultures. An increase in production of the myofibroblast-associated splice variant of fibronectin (EDA-Fn) was seen in myofibroblast 3D cultures. Because the regulation of procollagen I processing is known to have profound effects on ECM assembly, differences in procollagen I secretion and maturation coupled with expression of EDA-Fn are shown to contribute to the production of a distinct ECM by the cardiac myofibroblast.

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“…32 Increased activation of TGF-b has also been demonstrated for fibroblasts subjected to strain. 33 It was proposed that upregulation of type I collagen expression in response to cellular stresses is mediated by TGF-b stimulation. 34 This study is the first to document that ultrasound treatment stimulates secretion of TGF-b and collagen expression of tendon cells at the transcriptional level in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound stimulation of types I and III collagen expression of tendon cell and upregulation of transforming growth factor β

Tsai

Pang

Hsu

et al. 2006

Journal Orthopaedic Research

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Traumatic tendon injuries are commonly treated with ultrasound. However, previous research has not examined the molecular mechanism of this therapeutic effect on collagen synthesis of tendon cells. This study was designed to determine the effect of ultrasound on the expression of type I and type III collagen of tendon cells intrinsic to rat Achilles tendon. Whether a correlation exits between this effect and the expression of transforming growth factor b (TGF-b), which enhances collagen synthesis, was also investigated. Tendon cells after ultrasound treatment and protein expression of types I and III collagen were determined by immunocytochemistry. The mRNA expressions of a1(I) procollagen, a1(III) procollagen, and TGF-b were determined by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the concentration of TGF-b in conditioned medium was evaluated by enzyme-linked immunosorbent assay (ELISA). Immunocytochemical staining revealed that ultrasound-treated tendon cells were stained more strongly for types I and III collagen than were control cells. Upregulation of procollagen a1(I) gene, procollagen a1(III) gene, and TGF-b at the mRNA level was confirmed by RT-PCR. A dose-dependent increase in the concentration of TGF-b in conditioned medium obtained from cells treated with ultrasound was demonstrated by ELISA assay (p ¼ 0.043). In conclusion, ultrasound stimulates the expression of type I and type III collagen in a process that is likely mediated by the upregulation of TGF-b. ß

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Differential Responses of Adult Cardiac Fibroblasts to in vitro Biaxial Strain Patterns

Cited by 139 publications

References 29 publications

Myocardial Fibrosis in Chronic Aortic Regurgitation

Myocardial Fibrosis in Chronic Aortic Regurgitation

Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition

Ultrasound stimulation of types I and III collagen expression of tendon cell and upregulation of transforming growth factor β

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