scholarly journals Telomere Length in Valve Tissue Is Shorter in Individuals With Aortic Stenosis and in Calcified Valve Areas

Author(s):  
Ilona Saraieva ◽  
Athanase Benetos ◽  
Carlos Labat ◽  
Anders Franco-Cereceda ◽  
Magnus Bäck ◽  
...  

BackgroundShort telomere length (TL) is associated with age-related diseases, in particular cardiovascular diseases. However, whether the onset and course of aortic stenosis (AS) is linked to TL in aortic valves remains unknown.ObjectivesTo assess telomere dynamics (TL and telomerase activity) in aortic valves and the possible implication of TL in onset and course of AS.MethodsDNA was extracted from aortic valves obtained from 55 patients (78.2% men; age, 37–79 years), who had undergone replacement surgery due to AS (AS group, n = 32), aortic valve regurgitation and aortic dilation (Non-AS group, n = 23). TL was measured by telomere restriction fragment analysis (TRF) in calcified and non-calcified aortic valve areas. Telomerase activity was evaluated using telomerase repeat amplification protocol (TRAP) in protein extracts from non-calcified and calcified areas of valves obtained from 4 additional patients (50% men; age, 27–70 years).ResultsTL was shorter in calcified aortic valve areas in comparison to non-calcified areas (n = 31, 8.58 ± 0.73 kb vs. 8.12 ± 0.75 kb, p < 0.0001), whereas telomerase activity was not detected in any of those areas. Moreover, patients from AS group displayed shorter telomeres in non-calcified areas than those from the Non-AS group (8.40 ± 0.64 kb vs. 8.85 ± 0.65, p = 0.01).ConclusionsShort telomeres in aortic valves may participate in the development of AS, while concurrently the calcification process seems to promote further local decrease of TL in calcified areas of valves.

Author(s):  
Glenn R. Barnhart ◽  
Malakh Lal Shrestha

Aortic stenosis is the most common valvular heart disease in the Western world. It is caused primarily by age-related degeneration and progressive calcification typically detected in patients 65 years and older. In patients presenting with symptoms of heart failure, the average survival rate is only 2 years without appropriate treatment. Approximately one half of all patients die within the first 2 to 3 years of symptom onset. In addition, the age of the patients presenting for aortic valve replacement (AVR) is increased along with the demographic changes. The Society of Thoracic Surgeons (STS) database shows that the number of patients older than 80 years has increased from 12% to 24% during the past 20 years. At the same time, the percentage of candidates requiring AVR as well as concomitant coronary bypass surgery has increased from 5% to 25%. Surgical AVR continues to be the criterion standard for treatment of aortic stenosis, improving survival and quality of life. Recent advances in prosthetic valve technology, such as transcatheter AVR, have expanded the indication for AVR to the extreme high-risk population, and the most recent surgical innovation, rapid deployment AVR, provides an additional tool to the surgeons’ armamentarium.


2016 ◽  
Vol 20 (4) ◽  
pp. 83 ◽  
Author(s):  
E. I. Kretov ◽  
K. V. Kozyr ◽  
A. R. Tarkova ◽  
D. S. Sergeevichev ◽  
A. A. Korobeynikov ◽  
...  

<p>Calcific aortic stenosis is an aortic valve disease of atherosclerotic origin occurring in 2-4 % of persons older than 65 years, for whom open surgery is contraindicated. Models of self-expanding aortic valves available today have a number of significant drawbacks. The authors have developed a prototype of a new aortic valve and present its first successful implantation in the experiment.</p><p>Received 17 October 2016. Accepted 22 November 2016.</p><p><strong>Funding:</strong> The study had no sponsorship.<br /><strong>Conflict of interest:</strong> The authors declare no conflict of interest.</p>


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kopytek ◽  
R Kolasa-Trela ◽  
M Zabczyk ◽  
A Undas ◽  
J Natorska

Abstract Background High hemodynamic forces similar to those observed in aortic stenosis (AS) can trigger neutrophil extracellular traps (NETs) formation. Purpose An involvement of NETosis in the AS pathogenesis is unknown. Methods We enrolled 25 patients, median age 64.9 [range, 58–69] years with isolated severe AS (transvalvular pressure gradient, PGmean: 53.6±11.3 mm Hg, PGmax: 85.1±17.6 mmHg), after aortic valve replacement and 15 healthy sex/age-matched controls. Autopsy-derived aortic valves from 5 healthy donors served as negative control. Transverse valve sections were taken from the mid and commissural areas of the leaflet and cryosectioned by a Leica CM 1520 cryostat. Valvular expression of citrullinated histone H3 (citH3), together with myeloperoxidase (MPO), and neutrophil elastase (NE) as NETs biomarkers and macrophages (CD68) were evaluated by single- and double- immunostaining. Plasma concentrations of citH3 and interleukin 6 (IL-6) were also determined. Results All stenotic and healthy valves expressed citH3 in the leaflets' endothelial and sub-endothelial layers at the aortic side. The in loco expression of citH3-positive cells was higher in AS patients compared with controls (42.3±8.7% vs. 7.2±4.8%, p<0.05) and correlated with disease severity measured as aortic valve area (AVA; r=−0.84, p<0.0001), as well as PGmean (r=0.62, p<0.001), and PGmax (r=0.52, p>0.05). Double-staining revealed that within stenotic leaflets 28.3±8.4% of cells were citH3/MPO- and 25.2±7.1% citH3/NE-positive. None of control valves showed MPO or NE-positivity. Moreover, 6.6±1.9% of valvular cells (17.2±5.4% of citH3-positive cells) showed citH3/CD68 double-positivity and were identified as macrophages. Plasma levels of citH3 were 59% higher in AS patients then in controls (p<0.05), and the concentrations of citH3 correlated with IL-6 levels (r=0.44, p<0.05) and AVA (r=−0.48, p<0.05). Conclusions The presence of NETs in stenotic valves and association with AS severity might suggest novel mechanisms involved in the disease progression. This work was supported by the grant from the Polish National Science Center (DEC-2017/01/X/NZ5/02006 to R.K-T.). Acknowledgement/Funding This work was supported by the grant from the Polish National Science Center (DEC-2017/01/X/NZ5/02006 to R.K-T.).


2015 ◽  
Vol 27 (1) ◽  
pp. 109
Author(s):  
G. A. Kim ◽  
H. J. Oh ◽  
M. J. Kim ◽  
Y. K. Jo ◽  
E. M. N. Setyawan ◽  
...  

Telomerase is important ribonucleoprotein for restoring telomere length from its own RNA template. Regarding cloned animals derived from somatic cell nuclear transfer (SCNT), interesting questions have been raised about whether the cloning process restores cellular telomerase activity undergone by their donor cells. The present study was conducted to determine the effects of cloning on telomerase activity in the dog and normality of telomerase activity in cloned dogs. Focusing our attention on differences in telomerase activity depending on the age, we analysed telomerase activity in dogs produced by natural breeding of various ages. Comparison of the telomerase activities of cloned dogs and those of dogs produced by natural breeding was also performed. For SCNT, 2 cell donors, 7- and 9-year-old beagles, were used and donor cells were isolated from ear skin. After establishing donor cell lines, the enucleated canine in vivo-matured oocytes and the cells were injected and fused by electrofusion. After 30 days from embryo transfer, pregnancy diagnosis was performed and 7 cloned dogs were produced on the due date. For standardization of telomerase activity in beagles produced by natural breeding, blood of total 14 dogs at each age (10 months, 20 months, 5, 7, and 8 years old) were collected and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP) assay. Telomerase activity measurements of at least 6 replications in each dog were performed. For statistical analysis, one-way ANOVA with Dunn's Multiple Comparison Test was used. Significant differences in telomerase activity were observed between the blood of cloned and donor dogs. It was shown that mean telomerase activities were decreased according to biological aging with significances. Mean telomerase activities in 10 cloned dogs were higher than those of a donor dog. Cloned dogs also showed similar levels of telomerase activities as their age-matched natural bred dogs, suggesting that they are within the variation in normal dogs. These observations indicate that the cloning process restores the telomerase activity in the dog. Thus, complex regulation of telomerase activity during nuclear reprogramming may regulate and be involved in telomerase activity in cloned dogs. It remains to be determined whether telomere length is correlated with telomerase activity and if it accurately reflects the physiological age of cloned dogs.This study was supported by IPET (#311062–04–2-SB010), RDA (PJ008975022013), Research Institute for Veterinary Science, the BK21 program, Nestle Purina Korea, and TS Corporation.


2011 ◽  
Vol 57 (14) ◽  
pp. E1312
Author(s):  
Sophie Pierard ◽  
Christophe de Meester ◽  
Stéphanie Seldrum ◽  
David Vancraeynest ◽  
Agnès Pasquet ◽  
...  

Author(s):  
Aileen Murphy ◽  
Elisabeth Fenwick ◽  
William D. Toff ◽  
Matthew P. Neilson ◽  
Colin Berry ◽  
...  

Aortic stenosis (AS) is caused by age-related calcific degeneration of the aortic valve (1). Initially, cases are asymptomatic but, from the point that symptoms first develop, there is rapid progression and if left untreated survival estimates are low (2–3 years) (1). Therefore, managing AS effectively and efficiently is a priority for health systems with increasing healthcare costs and longer life expectancy.


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