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

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.

Author(s):  
Gabbar Jadhav

In this paper we discussed the heart valve disease. This heart valve disease occur throughout the world due to the more ethical estimation and grow curator of heart valve diseases use the diagnosis for this type of valve disease . Actually Phonocardiogram (PCG) signals are used because it having less price and acquire the signals. In this we learn five different kind of heart areas, Also typical are aortic stenosis, mitral valve prolapse, mitral stenosis and mitral regurgitation.


2016 ◽  
pp. 20-24
Author(s):  
Bang Giap Vo ◽  
Anh Binh Ho ◽  
Van Minh Huynh

Objectives: To investigate the features of coronary artery lesions in patients over 50 with heart valve diseases and to find out the relationship between the levels of coronary artery lesions and heart valve diseases. Results: In patients over 50 year old with heart valve diseases, the rate of significant coronary artery lesions is 55.5%. In which, significant lesions in the group of both mitral and aorta valve diseases is 44.19%, only mitral valve diseases is of 70%, only aortic valve diseases is of 51.85%. There is a relationship between the severity of mitral valve diseases and right coronary artery lesions (OR 3.74: 1.64 to 8.5, p = 0.0017) and circumflex coronary artery lesions (OR 2.59: 1.16 to 5.75, p = 0.0192). The severity of heart valve lesions in significant coronary artery lesions group is higher than insignificant coronary artery lesions group or normal group. Conclusion: Coronary artery lesions is common in patients > 50 years old with heart valve diseases, there is a relationship between the severity of mitral valve diseases and and right coronary artery lesions and circumflex coronary artery lesions. Key words: coronary artery lesions, mitral valvediseases


2017 ◽  
Vol 313 (1) ◽  
pp. H14-H23 ◽  
Author(s):  
Kareem Salhiyyah ◽  
Padmini Sarathchandra ◽  
Najma Latif ◽  
Magdi H. Yacoub ◽  
Adrian H. Chester

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.


2021 ◽  
Author(s):  
Mengyue Hu ◽  
Xu Peng ◽  
Yang Zhao ◽  
Xiaoshuang Yu ◽  
Can Cheng ◽  
...  

To conveniently and effectively cure heart valve diseases or defects, combining with transcatheter valve technology, bioprosthetic heart valves (BHVs) originated from the decellularized porcine pericardium (D-PP) have been broadly used...


Author(s):  
Mostafa A. Salama ◽  
Aboul Ella Hassanien ◽  
Jan Platos ◽  
Aly A. Fahmy ◽  
Vaclav Snasel

2014 ◽  
Vol 72 ◽  
pp. 146-156 ◽  
Author(s):  
Diala El Husseini ◽  
Marie-Chloé Boulanger ◽  
Ablajan Mahmut ◽  
Rihab Bouchareb ◽  
Marie-Hélène Laflamme ◽  
...  

Author(s):  
Patrizio Lancellotti ◽  
Julien Magne ◽  
Kim O’Connor ◽  
Luc A. Pierard

Native mitral valve disease is the second valvular heart disease after aortic valve disease. For the last few decades, two-dimensional Doppler echocardiography was the cornerstone technique for evaluating patients with mitral valve disease. Besides aetiological information, echocardiography allows the description of valve anatomy, the assessment of disease severity, and the description of the associated lesions.This chapter will address the echocardiographic evaluation of mitral regurgitation (MR) and mitral stenosis (MS).In MR, the following findings should be assessed: 1. Aetiology. 2. Type and extent of anatomical lesions and mechanisms of regurgitation. 3. The possibility of mitral valve repair. 4. Quantification of MR severity. 5. Quantification of MR repercussions.In MS, the following findings should be assessed: 1. Aetiology. 2. Type and extent of anatomical lesions. 3. Quantification of MS severity. 4. Quantification of MS repercussions. 5. Wilkins or Cormier scores for the possibility of percutaneous mitral commissuroplasty.Management of patients with mitral valve disease is currently based on symptoms and on echocardiographic evaluation at rest. Therefore, knowing how to assess the severity of valve diseases as well as the pitfalls and the limitations of each echocardiographic method is of primary importance.


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