scholarly journals Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells

2017 ◽  
Vol 313 (1) ◽  
pp. H14-H23 ◽  
Author(s):  
Kareem Salhiyyah ◽  
Padmini Sarathchandra ◽  
Najma Latif ◽  
Magdi H. Yacoub ◽  
Adrian H. Chester
Keyword(s):  
Extracellular Matrix ◽  
Mitral Valve ◽  
Heart Valve ◽  
Potential Role ◽  
Complex Function ◽  
Interstitial Cells ◽  
Matrix Remodeling ◽  
Mechanical Stimuli ◽  
Valve Interstitial Cells

The sophisticated function of the mitral valve depends to a large extent on its extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important stimulus is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVICs) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulfated glycosaminoglycans (sGAG) in cultured porcine MVICs. Increased gene expression of matrix metalloproteinases-1 and -9 and their tissue inhibitors 1 and 2 was also observed after incubation under hypoxic conditions for up to 24 h. Hypoxia had no effect on MVIC viability, morphology, or phenotype. MVICs expressed hypoxia-inducible factor (HIF)-1α under hypoxia. Stimulating HIF-1α chemically caused a reduction in the amount of sGAG produced, similar to the effect observed under hypoxia. Human rheumatic valves had greater expression of HIF-1α compared with normal or myxomatous degenerated valves. In conclusion, hypoxia affects the production of certain ECM proteins and expression of matrix remodeling enzymes by MVICs. The effects of hypoxia appear to correlate with the induction of HIF-1α. This study highlights a potential role of hypoxia and HIF-1α in regulating the mitral valve, which could be important in health and disease. NEW & NOTEWORTHY This study demonstrates that hypoxia regulates extracellular matrix secretion and the remodeling potential of heart valve interstitial cells. Expression of hypoxia-induced factor-1α plays a role in these effects. These data highlight the potential role of hypoxia as a physiological mediator of the complex function of heart valve cells.

Abstract 319: Tnf-α and Il-1β Decrease Myofibroblast Differentiation in 3d-cultured Mitral Valve Interstitial Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Amadeus Zhu ◽  
Jane Grande-Allen
Keyword(s):  
Smooth Muscle ◽  
Mitral Valve ◽  
Heart Valve ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Tissue Type ◽  
Heart Valve Diseases ◽  
Valve Interstitial Cells ◽  
Tnf Α ◽  
Valve Diseases

Background: Fibrosis contributes to many heart valve diseases such as calcific aortic valve disease, rheumatic heart disease, and secondary mitral regurgitation. Heart valve leaflets are populated by quiescent, fibroblast-like valve interstitial cells (VICs). During fibrosis, VICs differentiate into activated, myofibroblast-like cells that adversely remodel the extracellular matrix. Activated VICs overexpress α-smooth muscle actin (ACTA2/αSMA) and smooth muscle 22-α (TAGLN/SM22α) and display increased contractility. Tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) have been reported to either promote or inhibit fibrosis, depending on tissue type. Understanding how TNF-α and IL-1β affect VIC activation in the mitral valve of the heart could enable development of pharmaceutical treatments for heart valve diseases, which are currently managed surgically. Methods: To avoid artifactual activation on tissue culture plastic, VICs were encapsulated in biomimetic scaffolds consisting of polyethylene glycol (4% w/v) functionalized with protease-degradable (GGGPQGIWGQGK) and integrin-binding (RGDS) peptides. These 3D cultures were treated with 10 ng/ml TNF-α, 10 ng/ml IL-1β, or vehicle for 2 days in low-serum (1%) media. RNA and protein were measured via qRT-PCR, western blotting, and immunostaining. To measure contractility, VICs were encapsulated in collagen I (2.5 mg/ml) gels and allowed to contract freely for 2 days. Results: TNF-α and IL-1β significantly decreased RNA expression of ACTA2 (TNF-α: -91±6%, IL-1β: -99±1% change vs. vehicle) and TAGLN (TNF-α: -77±9%, IL-1β: -93±1% change). TNF-α and IL-1β also significantly decreased αSMA protein expression (TNF-α: -76±11%, IL-1β: -91±5% change) and the percentage of αSMA-positive cells (vehicle: 21±3%, TNF-α: 13±2%, IL-1β: 13±5% positive). Finally, TNF-α and IL-1β attenuated VIC-mediated collagen gel contraction (vehicle: 81±7%, TNF-α: 71±3%, IL-1β: 61±4% contraction). Conclusions: TNF-α and IL-1β decrease VIC activation in a 3D culture model of the mitral valve. These results reveal novel pathway targets for reducing fibrosis during mitral valve disease. Future work will use this model to study the downstream signaling events that drive VIC de-activation.

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

A potential role for the CDH13/CDH15 gene in repeat revascularization after first percutaneous coronary intervention

2020 ◽  
Vol 21 (2) ◽  
pp. 91-99
Author(s):  
Qian Xiang ◽  
Zhiyan Liu ◽  
Yun Lu ◽  
Jie Mao ◽  
Shuqing Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Percutaneous Coronary Intervention ◽  
Potential Role ◽  
Coronary Intervention ◽  
Repeat Revascularization ◽  
Genetic Test Results ◽  
Percutaneous Coronary ◽  
Matrix Interactions ◽  
Extracellular Matrix Interactions

Aim: Major drawbacks of percutaneous coronary intervention are the high occurrence of repeat revascularization due to restenosis and disease progression. The aim of this study was to find genetic indicators to predict the risk of repeat revascularization. Materials & methods: From April 2015 to June 2016, 143 patients with percutaneous coronary intervention with genetic test results were enrolled. SNPs were measured by OmniZhongHua-8, and the SNPs in pathways genes related to known stenosis-related processes from the KEGG, BioCarta and Gene Cards databases were selected for analysis. Results: Cell–extracellular matrix interactions were the pathways with the most significant SNP ( CDH15 rs72819363) association with repeat revascularization. Compared with CDH13 rs11859453G carriers, the adjusted odds ratio for A carriers was 0.25 and 0.33 at 18 and 30 months. Conclusion: We demonstrated a potential role of the cell–extracellular matrix interactions pathway and the possible biomarker CDH13/CDH15 in the development of coronary repeat revascularization.

scholarly journals A Potential Role for MMPs during the Formation of Non-Neurogenic Placodes

2018 ◽  
Vol 6 (3) ◽  
pp. 20 ◽  
Author(s):  
Paige Drake ◽  
Tamara Franz-Odendaal
Keyword(s):  
Extracellular Matrix ◽  
Mammary Gland ◽  
Matrix Metalloproteinases ◽  
Potential Role ◽  
Critical Role ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Lens Development ◽  
Cell Behaviors ◽  
Placode Formation

The formation of non-neurogenic placodes is critical prior to the development of several epithelial derivatives (e.g., feathers, teeth, etc.) and their development frequently involves morphogenetic proteins (or morphogens). Matrix metalloproteinases (MMPs) are important enzymes involved in extracellular matrix remodeling, and recent research has shown that the extracellular matrix (ECM) can modulate morphogen diffusion and cell behaviors. This review summarizes the known roles of MMPs during the development of non-neurogenic structures that involve a placodal stage. Specifically, we discuss feather, hair, tooth, mammary gland and lens development. This review highlights the potential critical role MMPs may play during placode formation in these systems.

Abstract 311: The Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling

2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Marika Fava ◽  
Javier Barallobre-Barreiro ◽  
Ursula Mayr ◽  
Ruifang Lu ◽  
Athanasios Didangelos ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Remodeling ◽  
Aortic Dilatation ◽  
Matrix Remodeling

scholarly journals Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 409 ◽  
Author(s):  
Manuela Antoniel ◽  
Francesco Traina ◽  
Luciano Merlini ◽  
Davide Andrenacci ◽  
Domenico Tigani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Critical Role ◽  
Active Form ◽  
Congenital Muscular Dystrophy ◽  
Cell Polarization ◽  
Pcr Analysis ◽  
Matrix Remodeling ◽  
Collagen Vi

Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.

scholarly journals Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling

2018 ◽  
Vol 38 (7) ◽  
pp. 1537-1548 ◽  
Author(s):  
Marika Fava ◽  
Javier Barallobre-Barreiro ◽  
Ursula Mayr ◽  
Ruifang Lu ◽  
Athanasios Didangelos ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Remodeling ◽  
Aortic Dilatation ◽  
Matrix Remodeling
Sign in / Sign up

Export Citation Format

Share Document