scholarly journals Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves

2016 ◽  
Vol 13 (125) ◽  
pp. 20160449 ◽  
Author(s):  
Matthew C. Sapp ◽  
Varun K. Krishnamurthy ◽  
Daniel S. Puperi ◽  
Saheba Bhatnagar ◽  
Gabrielle Fatora ◽  
...  

Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves. During fibrotic valve disease, leaflet thickening due to abnormal extracellular matrix is likely to reduce regional oxygen availability. To assess the impact of low oxygen levels on valve behaviour, whole leaflet organ cultures were created to induce leaflet hypoxia. These studies revealed a loss of layer stratification and elevated levels of hypoxia inducible factor 1-alpha in both aortic and mitral valve hypoxic groups. Mitral valves also exhibited altered expression of angiogenic factors in response to low oxygen environments when compared with normoxic groups. Hypoxia affected aortic and mitral valves differently, and mitral valves appeared to show a stenotic, rheumatic phenotype accompanied by significant cell death. These results indicate that hypoxia could be a factor in mid to late valve disease progression, especially with the reduction in chondromodulin-1 expression shown by hypoxic mitral valves.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Viana ◽  
R M Vieira De Melo ◽  
D N V Da Silva ◽  
G P Santana ◽  
M L N De Paula ◽  
...  

Abstract Introduction Observational studies differ on the impact of performing tricuspid repair on surgical mortality. Some studies demonstrate increased surgical mortality related to right ventricular failure and circulatory shock, while there are other studies that evidence improvement in quality of life and signs of right heart failure in the long time. Objective To evaluate the impact on surgical mortality of concomitant tricuspid annuloplasty in patients undergoing cardiac surgery for rheumatic mitral valve disease, who have moderate to severe tricuspid regurgitation. Methods This is a prospective cohort from January 1, 2017 to December 30, 2020. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with moderate to significant tricuspid regurgitation were included. The primary outcome was 30-days mortality. Results 165 patients were included, 98 (59.4%) underwent tricuspid valve annuloplasty. The mean age was 46, 5 (±12) years, the median of Euroscore II was 2,33%. The 30-days mortality was 17 (10.3%) and there was no difference between the groups submitted or not to tricuspid repair: 12 (12.2%) versus 5 (7.5%); p=0.44, respectively. In the multivariate analysis involving seven variables with a potential prediction of death in 30 days, tricuspid repair had no association with death, RR 2,4 (0,5 – 8,3); p=0.27. Conclusion In patients with rheumatic heart disease undergoing cardiac surgery for rheumatic mitral valve disease, perform tricuspid annuloplasty in individuals who had moderate to severe tricuspid insufficiency was not associated with increased surgical mortality. FUNDunding Acknowledgement Type of funding sources: None.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B Zhang ◽  
H T Zhang ◽  
H Y Xu ◽  
Y J Wu

Abstract Background Valvular heart disease (VHD) has been caught in two important cross-currents in recent decades: aging demography and the rise of multimodality imaging and transcatheter valve therapy. In this setting, we aim to identify the distribution, characteristics, and management of Chinese VHD patients according to age. Methods China Valvular Heart Disease Cohort Study (China-VHD) was conducted from March to September 2019 in 46 centers over China. It included prospectively 12331 adults with native moderate or severe VHD, of which we described the distribution, management, and in-hospital events according to age (18–44, 45–54, 55–64, 65–74, ≥75). Multivariate Logistic regression was employed to investigate the impact of age on in-hospital events composed of in-hospital mortality, acute heart failure, and stoke. Results In Chinese VHD population, overall percentage peaked in 55–64 year olds. The frequency of multivalvular heart disease (MVHD) saw an increasing trend with age (p for trend <0.001). Of single valvular heart disease, mitral regurgitation (MR) was the most frequent left-sided VHD followed by aortic regurgitation (AR), aortic stenosis (AS), and mitral stenosis (MS). AS frequency significantly grew with age (p for trend = 0.02) while AR peaked in 18–44 year olds and fluctuated at a lower level in the older population. In contrast, mitral valve disease (MS, MR, and mixed mitral valve disease) was most frequent in 45–54 year olds and dropped with age (p for trend all <0.001). Noteworthily, all aortic valve disease was notably frequent in men whereas mitral valve disease and MVHD more common in women. Similar to developed countries, degenerative etiology rose steeply while rheumatic and congenital origin fell with age. Regarding management, surgical valve replacement rate was similar in age groups lower than 75 years old with increasing frequency of concomitant CABG. No matter aortic or mitral, the percentage of bio-prosthesis rocketed after 65 years (aortic: 74.7%, mitral: 70.6%). In multivariate logistic regression, covariables included age, sex, BMI, hypertension, diabetes, coronary heart disease, aortic disease, cardiomyopathy, COPD, NYHA class and valvular intervention. Compared to patients younger than 45, in-hospital events significantly higher in patients over 75 only (OR: 1.69 [95% CI: 1.07–2.66], p<0.02). Moreover, women showed a lower risk of in-hospital events (OR: 0.78 [95% CI: 0.63–0.96], p<0.01). Age distribution of VHD Conclusion Age plays a crucial role in valvular heart disease, best illustrated in AS. Unlike the western world, AR and MR are more frequent than AS but show a slightly decreasing trend with age. As expected, degenerative etiology is becoming more prevalent whereas rheumatism decreases. Age over 75 and male are associated with growing in-hospital events. Degenerative VHD thus present an important public-health burden. Acknowledgement/Funding Innovation project of Chinese academy of medical science


Author(s):  
Jean-Pierre Rabbah ◽  
Neelakantan Saikrishnan ◽  
Ajit P. Yoganathan

Patient specific mitral valve computational models are being actively developed to facilitate surgical planning. These numerical models increasingly employ more realistic geometries, kinematics, and mechanical properties, which in turn requires rigorous experimental validation [1]. However, to date, native mitral flow dynamics have not been accurately and comprehensively characterized. In this study, we used Stereoscopic Particle Image Velocimetry (SPIV) to characterize the ventricular flow field proximal to a native mitral valve in a pulsatile experimental flow loop.


Author(s):  
Claire Colebourn ◽  
Jim Newton

This chapter describes the pathophysiology and methods of assessment of valve lesions affecting the aortic and mitral valves. It describes the management of these valve lesions in the critical care setting and guides decision-making about the impact of the valve lesion on the critical illness. The diagnosis and management of infective endocarditis are described in detail.


Author(s):  
Lina Farhana Mahadi ◽  
Nabilah Ibrahim ◽  
Shahnoor Shanta ◽  
Hideyuki Hasegawa

<p><span style="font-family: 'Times New Roman',serif; font-size: 9pt; mso-bidi-font-size: 11.0pt; mso-fareast-font-family: 'Times New Roman'; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;" lang="EN-US"><span style="font-family: 'Times New Roman',serif; font-size: 9pt; mso-bidi-font-size: 11.0pt; mso-fareast-font-family: 'Times New Roman'; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;" lang="EN-US">Mitral valve movement is essential to be identified in order to monitor the abnormality of blood flow in right side of heart. The estimation and tracking of mitral valve has seldom been investigated since it required high temporal rate to scan the echocardiography images and it depends on the operator to capture the low-speckle and-noise images. This study presents the validation experiment performed on heart phantom made of t</span><span style="font-family: 'Times New Roman',serif; font-size: 9pt; mso-bidi-font-size: 10.0pt; mso-fareast-font-family: 'Times New Roman'; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;" lang="EN-US">hermoplastic polyurethane (TPU) filament which the objective is to validate the previous </span><span style="font-family: 'Times New Roman',serif; font-size: 9pt; mso-bidi-font-size: 11.0pt; mso-fareast-font-family: 'Times New Roman'; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;" lang="EN-US">features tracking technique implemented in mitral valve locating in video frames using Kanade-Lucas-Tomasi (KLT) algorithm. The outcome was able to automatically detect the edge of mitral valve and thus in future, it manages to predict the flowing of blood pattern. An in-vitro experiment was conducted which involved a valve phantom scanning in water tank that connected to water pump. It was found in this study that the technique capable to detect and visualize the mitral valve up to 59 frames in 2.36 secondsby tracking the features of minimum eigenvalue within the selected region. It was also produced a good agreement of valve distance between the true value and the measured one, which achieved the minimum of 88% similarity. This yielded the validation of the proposed technique to track and visualize the mitral valves. </span></span></p>


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michael A Hagler ◽  
Nassir M Thalji ◽  
Nate Russell ◽  
Michael Welge ◽  
Colleen Bushell ◽  
...  

Introduction: Myxomatous mitral valve disease (MMVD) is a degenerative condition characterized by tissue fibrosis and matrix remodeling which ultimately progresses to leaflet prolapse. While recent work has shown that transforming growth factor beta (TGF-β) signaling contributes to the pathogenesis of MMVD, upstream regulators of this and other pathways remain poorly understood. Hypothesis: We sought to use high-throughput RNA sequencing coupled with microRNA (miRNA) sequencing to identify novel molecular targets as well as upstream regulators contributing to MMVD. Methods: We conducted mRNA and miRNA sequencing on normal (n = 10) and myxomatous human mitral valve samples (n = 10). Differential expression was identified using linear modeling and parallel random forest analyses. Canonical pathways were identified by Ingenuity Pathway Analyses (IPA). Predicted miRNA targets were identified using TargetScanHuman 6.2. Results: We found 2784 mRNAs that were differentially expressed between normal and myxomatous mitral valves, which IPA largely categorized in to pro-fibrotic, matrix remodeling and cellular proliferation signaling. In miRNA sequenced from the same samples, 67 miRNAs were differentially-expressed between normal and myxomatous mitral valves. Increased expression of TGF-β ligands, collagen isoforms, and matrix metalloproteinases were associated with reductions in miRNAs predicted to target them. Conversely, mRNA levels of the “protective” genes TGFβ-induced factor homeobox 1, salt-inducible kinase 1, TIMP metallopeptidase inhibitor 4, and cyclin-dependent kinase inhibitor 1C mRNA levels were decreased in myxomatous tissue, and miRNAs predicted to target these genes (e.g., miR-656, miR-379-3p, miR-664a-3p, and miR-34c-5p) were significantly increased. Conclusions: Collectively, these data not only identify novel genes that are differentially regulated in MMVD, but also suggest miRNAs may play an active role in suppressing key protective molecules in MMVD. Thus, anti-mIRs therapy may be a viable therapeutic target to restore anti-fibrotic and anti-proliferative molecules in the valve and slow progression of MMVD. Future mechanistic studies will lay a critical foundation for translational work in these areas.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Alex Sahagian ◽  
Candice Dilworth ◽  
Elizabeth Robertson ◽  
Yaxin Lu ◽  
Murat Kekic ◽  
...  

Upregulated Transforming Growth Factor-beta (TGF-β) signaling has been implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) in both humans and canines. Moreover, it has been postulated that the phenotypic transformation of valve interstitial cells (VICs) in the mitral valve into alpha-smooth muscle actin (α-SMA)-positive myofibroblast-like cells contribute to elevated levels of proteolytic enzymes such as matrix metalloproteinases (MMPs), which subsequently induce pathological remodeling of the extracellular matrix (ECM) in the mitral valve. We hypothesized that, in MMVD, upregulation of TGF-β signaling would induce the transformation of VICs into myofibroblast-like cells, which subsequently express increased levels of MMPs. Computational immunohistochemistry was used to quantify protein expression in mitral valve leaflet tissue from canines affected by MMVD (n=4) and from control canines (n=5). TGF-β and α-SMA expression was significantly increased (p<0.001) in MMVD tissue compared to control tissue. Moreover, a significant positive correlation was found between TGF-β expression and α-SMA expression (p<0.05) across the entire cohort. There were also significant increases in MMP-2 and MMP-9 expression (p<0.05) in MMVD tissue compared to control tissue. No change in MMP-3 expression was detected. These findings are consistent with abnormal TGF-β signaling inducing the differentiation of VICs into α-SMA-positive myofibroblast-like cells. Moreover, the increases in expression of MMP-2 and MMP-9 in MMVD indicate the likely role of these myofibroblast-like cells in mediating pathological remodeling of the ECM throughout the disease process. The paradoxical finding of no change in MMP-3 expression may represent a compensatory mechanism that attempts to limit further degenerative damage to the mitral valve. In conclusion, MMVD is characterized by TGF-β-induced differentiation of VICs into myofibroblast-like cells, which subsequently facilitate ECM degradation via the increased expression of MMPs. This supports the rationale for the use of angiotensin II receptor blockers, capable of attenuating TGF-β signaling, in the treatment of MMVD.


2008 ◽  
Vol 22 (1) ◽  
pp. 57-62 ◽  
Author(s):  
A. Ates ◽  
O. Simsek ◽  
B. Ertugral ◽  
M. Ertugrul

The elemental analysis of mitral valves from 12 patients with rheumatic mitral valve disease was performed using radioisotope excited energy dispersive X-ray fluorescence (EDXRF) technique. An annular 50 mCi55Fe radioactive source was used for excitation of characteristic K X-rays of the trace elements in the samples. A high resolution Si(Li) detector, which has a 160 eV full width at half maximum for 5.9 keV photons, was used for intensity measurements. Concentrations of the elements P, S, K and Cl in the mitral valve samples were determined by using standard addition method. Deficiencies or excesses of these trace elements cause the valves to run irregularly. Abnormal value of these elements may also result in rheumatic valve disease.


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