Cardiac Valve Interstitial Cells: Regulator of Valve Structure and Function

Mulholland, Diane; Gotlieb, Avrum I.

doi:10.1016/s1054-8807(96)00115-9

Cited by 41 publications

(30 citation statements)

References 26 publications

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“…VICs closely resemble myofibroblasts, which are found in many tissues and play important roles in tissue remodeling [12,13]. Additionally, VICs actively participate in the response to injury and promote valve repair [14], and they are also responsible for the synthesis and remodeling of the extracellular matrix (ECM) components of the valve [11,15]. A significant challenge in the synthesis of a tissue-engineered valve has been the re-creation of the appropriate ECM distribution and composition [16].…”

Section: Introductionmentioning

confidence: 99%

Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells

et al. 2005

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Section: Introductionmentioning

confidence: 99%

Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells

et al. 2005

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“…1 Under normal circumstances, VICs are quiescent and maintain the structural integrity and function of the valve. 2,3 In response to valve injury, VICs undergo phenotypic changes and become activated. 4,5 ␣-Smooth muscle actin (␣-SMA), a cytoskeletal isoform of actin not normally found in the quiescent VICs of normal heart valves, is a marker for activated VICs.…”

mentioning

confidence: 99%

Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Liu

Gotlieb

2008

The American Journal of Pathology

100

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The regulation of valve interstitial cell (VIC) function in response to tissue injury and valve disease is not well understood. Because transforming growth factor-␤ (TGF-␤) has been implicated in tissue repair, we tested the hypothesis that TGF-␤ is a regulator of VIC activation and associated cell responses that occur during early repair processes. We used a well-characterized wound model that was created by mechanical denudation of a confluent VIC monolayer to study activation and repair 24 hours after wounding. VIC activation was demonstrated by immunofluorescent localization of ␣-smooth muscle actin (␣-SMA), and ␣-SMA mRNA levels were quantified by real-time polymerase chain reaction. Proliferation and apoptosis were quantified by bromodeoxyuridine staining and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Repair was quantified by measuring VIC extension into the wound , and TGF-␤ expression was shown by immunofluorescent localization of intracellular TGF-␤. Compared with nonwounded monolayers, VICs at the wound edge showed ␣-SMA staining, increased ␣-SMA mRNA content, elongation into the wound with stress fibers, proliferation, and apoptosis. VICs at the wound edge also showed increased TGF-␤ and pSmad2/3 staining with co-expression of ␣-SMA. Addition of TGF-␤ neutralizing antibody to the wound decreased VIC activation, ␣-SMA mRNA content, proliferation, apoptosis, wound closure rate, and stress fibers. Conversely, exogenous addition of TGF-␤ to the wound increased VIC activation , proliferation , wound closure rate , and stress fibers. Thus , wounding activates VICs , and TGF-␤ signaling modulates VIC response to injury.

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“…Valvular interstitial cells (VICs) are the most prevalent cells of heart valve leaflets and are responsible for maintaining the structural integrity of the valve. [1][2][3] In addition to a cellular component, valve leaflets are comprised of extracellular matrix (ECM) proteins, primarily collagen, elastin, and glycosoaminoglycans, arranged exquisitely to achieve a structure that is flexible enough to change shape easily, yet strong enough to withstand elevated hemodynamic stress. 4 Valve structure maintenance requires proper ECM metabolism, a function attributed to VICs.…”

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confidence: 99%

Valvular Myofibroblast Activation by Transforming Growth Factor-β

Walker

Masters

Shah

et al. 2004

Circulation Research

353

177

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Abstract-The pathogenesis of cardiac valve disease correlates with the emergence of muscle-like fibroblasts (myofibroblasts). These cells display prominent stress fibers containing ␣-smooth muscle actin (␣-SMA) and are believed to differentiate from valvular interstitial cells (VICs). However, the biological factors that initiate myofibroblast differentiation and activation in valves remain unidentified. We show that transforming growth factor-␤1 (TGF-␤1) mediates differentiation of VICs into active myofibroblasts in vitro in a dose-dependent manner, as determined by a significant increase in ␣-SMA and the dramatic augmentation of stress fiber formation and alignment. Additionally, TGF-␤1 and increased mechanical stress function synergistically to enhance contractility. In turn, contractile valve myofibroblasts exert tension on the extracellular matrix, resulting in a dramatic realignment of extracellular fibronectin fibrils. TGF-␤1 also inhibits valve myofibroblast proliferation without enhancing apoptosis. Our results are consistent with activation of a highly contractile myofibroblast phenotype by TGF-␤1 and are the first to connect valve myofibroblast contractility with pathological valve matrix remodeling. We suggest that the activation of contractile myofibroblasts by TGF-␤1 may be a significant first step in promoting alterations to the valve matrix architecture that are evident in valvular heart disease.

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Cardiac Valve Interstitial Cells: Regulator of Valve Structure and Function

Cited by 41 publications

References 26 publications

Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells

Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells

Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Valvular Myofibroblast Activation by Transforming Growth Factor-β

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