Saraieva Ilona, Benetos Athanase, Labat Carlos, Franco-Cereceda Anders, Bäck Magnus, Toupance Simon
INSERM, DCAC, Université de Lorraine, Nancy, France.
CHRU-Nancy, Pôle "Maladies du Vieillissement, Gérontologie et Soins Palliatifs", Université de Lorraine, Nancy, France.
Front Cell Dev Biol. 2021 Mar 11;9:618335. doi: 10.3389/fcell.2021.618335. eCollection 2021.
Short 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.
To assess telomere dynamics (TL and telomerase activity) in aortic valves and the possible implication of TL in onset and course of AS.
DNA 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, = 32), aortic valve regurgitation and aortic dilation (Non-AS group, = 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).
TL was shorter in calcified aortic valve areas in comparison to non-calcified areas ( = 31, 8.58 ± 0.73 kb vs. 8.12 ± 0.75 kb, < 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, = 0.01).
Short 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.
端粒长度缩短与年龄相关疾病有关,尤其是心血管疾病。然而,主动脉瓣狭窄(AS)的发病和病程是否与主动脉瓣端粒长度相关仍不清楚。
评估主动脉瓣端粒动力学(端粒长度和端粒酶活性)以及端粒长度在AS发病和病程中的可能影响。
从55例患者(男性占78.2%;年龄37 - 79岁)的主动脉瓣中提取DNA,这些患者因AS接受了置换手术(AS组,n = 32),或因主动脉瓣反流和主动脉扩张接受手术(非AS组,n = 23)。通过端粒限制片段分析(TRF)测量钙化和非钙化主动脉瓣区域的端粒长度。使用端粒酶重复扩增协议(TRAP)评估另外4例患者(男性占50%;年龄27 - 70岁)瓣膜非钙化和钙化区域蛋白质提取物中的端粒酶活性。
与非钙化区域相比,钙化主动脉瓣区域的端粒长度更短(n = 31,8.58 ± 0.73 kb对8.12 ± 0.75 kb,P < 0.0001),而在这些区域均未检测到端粒酶活性。此外,AS组患者非钙化区域的端粒比非AS组患者的短(8.40 ± 0.64 kb对8.85 ± 0.65,P = 0.01)。
主动脉瓣端粒缩短可能参与AS的发生发展,同时钙化过程似乎促进瓣膜钙化区域端粒长度进一步局部缩短。