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

Ilona Saraieva,Simon Toupance,Anders Franco-Cereceda,Athanase Benetos,Magnus Bäck,Carlos Labat

doi:10.3389/fcell.2021.618335

Abstract

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.

Highlights

Aortic stenosis (AS), the most common valvulopathy among the aging population in developed countries, affects both tricuspid and bicuspid valves (Roberts and Ko, 2005; Huntley et al, 2018)
telomere length (TL) was measured in aortic valves from 55 patients (Supplementary Figure 1)
Our results revealed that aortic valve areas with macroscopic calcifications displayed shorter telomeres compared with areas without calcifications within the same valve

Summary

Introduction

Aortic stenosis (AS), the most common valvulopathy among the aging population in developed countries, affects both tricuspid and bicuspid valves (Roberts and Ko, 2005; Huntley et al, 2018). Telomere Dynamics in Aortic Stenosis over 75 years (Nkomo et al, 2006). Calcific deposition in the leaflets is an active and highly regulated process, which involves mechanisms similar to those of atherosclerotic cardiovascular disease (ASCVD) (Mathieu and Boulanger, 2014; Pawade et al, 2015). The pathogenesis of both diseases include lipid infiltration, chronic inflammation, and calcification (Mathieu and Boulanger, 2014; Pawade et al, 2015). Whether the onset and course of aortic stenosis (AS) is linked to TL in aortic valves remains unknown

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