Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225785140> ?p ?o ?g. }
- W4225785140 endingPage "1890" @default.
- W4225785140 startingPage "1876" @default.
- W4225785140 abstract "The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), has protective functions in the cardiovascular system. TERT is not only present in the nucleus but also in mitochondria. However, it is unclear whether nuclear or mitochondrial TERT is responsible for the observed protection, and the appropriate tools are missing to dissect this.We generated new mouse models containing TERT exclusively in the mitochondria (mitoTERT mice) or the nucleus (nucTERT mice) to finally distinguish between the functions of nuclear and mitochondrial TERT. Outcome after ischemia/reperfusion, mitochondrial respiration in the heart, and cellular functions of cardiomyocytes, fibroblasts, and endothelial cells, as well, were determined.All mice were phenotypically normal. Although respiration was reduced in cardiac mitochondria from TERT-deficient and nucTERT mice, it was increased in mitoTERT animals. The latter also had smaller infarcts than wild-type mice, whereas nucTERT animals had larger infarcts. The decrease in ejection fraction after 1, 2, and 4 weeks of reperfusion was attenuated in mitoTERT mice. Scar size was also reduced and vascularization increased. Mitochondrial TERT protected a cardiomyocyte cell line from apoptosis. Myofibroblast differentiation, which depends on complex I activity, was abrogated in TERT-deficient and nucTERT cardiac fibroblasts and completely restored in mitoTERT cells. In endothelial cells, mitochondrial TERT enhanced migratory capacity and activation of endothelial nitric oxide synthase. Mechanistically, mitochondrial TERT improved the ratio between complex I matrix arm and membrane subunits, explaining the enhanced complex I activity. In human right atrial appendages, TERT was localized in mitochondria and there increased by remote ischemic preconditioning. The telomerase activator TA-65 evoked a similar effect in endothelial cells, thereby increasing their migratory capacity, and enhanced myofibroblast differentiation.Mitochondrial, but not nuclear TERT, is critical for mitochondrial respiration and during ischemia/reperfusion injury. Mitochondrial TERT improves complex I subunit composition. TERT is present in human heart mitochondria, and remote ischemic preconditioning increases its level in those organelles. TA-65 has comparable effects ex vivo and improves the migratory capacity of endothelial cells and myofibroblast differentiation. We conclude that mitochondrial TERT is responsible for cardioprotection, and its increase could serve as a therapeutic strategy." @default.
- W4225785140 created "2022-05-05" @default.
- W4225785140 creator A5001520142 @default.
- W4225785140 creator A5011792926 @default.
- W4225785140 creator A5015739454 @default.
- W4225785140 creator A5022712399 @default.
- W4225785140 creator A5026182510 @default.
- W4225785140 creator A5035502859 @default.
- W4225785140 creator A5035620570 @default.
- W4225785140 creator A5045160257 @default.
- W4225785140 creator A5046337325 @default.
- W4225785140 creator A5048399752 @default.
- W4225785140 creator A5060151311 @default.
- W4225785140 creator A5061950827 @default.
- W4225785140 creator A5065018686 @default.
- W4225785140 creator A5065167900 @default.
- W4225785140 creator A5074434578 @default.
- W4225785140 creator A5076009391 @default.
- W4225785140 creator A5076082024 @default.
- W4225785140 creator A5080194664 @default.
- W4225785140 creator A5080691366 @default.
- W4225785140 creator A5081723201 @default.
- W4225785140 creator A5089998359 @default.
- W4225785140 creator A5090828942 @default.
- W4225785140 date "2021-12-07" @default.
- W4225785140 modified "2023-10-14" @default.
- W4225785140 title "Mitochondrial Telomerase Reverse Transcriptase Protects From Myocardial Ischemia/Reperfusion Injury by Improving Complex I Composition and Function" @default.
- W4225785140 cites W1768274470 @default.
- W4225785140 cites W1979210673 @default.
- W4225785140 cites W1985348238 @default.
- W4225785140 cites W1991425040 @default.
- W4225785140 cites W1994446230 @default.
- W4225785140 cites W1996920927 @default.
- W4225785140 cites W1997655932 @default.
- W4225785140 cites W2001329934 @default.
- W4225785140 cites W2003578107 @default.
- W4225785140 cites W2009448733 @default.
- W4225785140 cites W2032781637 @default.
- W4225785140 cites W2037192636 @default.
- W4225785140 cites W2086007966 @default.
- W4225785140 cites W2087484885 @default.
- W4225785140 cites W2096313096 @default.
- W4225785140 cites W2099540110 @default.
- W4225785140 cites W2102774255 @default.
- W4225785140 cites W2120533799 @default.
- W4225785140 cites W2129462206 @default.
- W4225785140 cites W2139808613 @default.
- W4225785140 cites W2153060970 @default.
- W4225785140 cites W2153171315 @default.
- W4225785140 cites W2155112342 @default.
- W4225785140 cites W2159524064 @default.
- W4225785140 cites W2170097588 @default.
- W4225785140 cites W2201138959 @default.
- W4225785140 cites W2341782571 @default.
- W4225785140 cites W2436556612 @default.
- W4225785140 cites W2534893150 @default.
- W4225785140 cites W2767701190 @default.
- W4225785140 cites W2800350399 @default.
- W4225785140 cites W2802360440 @default.
- W4225785140 cites W2809289941 @default.
- W4225785140 cites W2809751535 @default.
- W4225785140 cites W2883109078 @default.
- W4225785140 cites W2886663158 @default.
- W4225785140 cites W2890607587 @default.
- W4225785140 cites W3038341522 @default.
- W4225785140 cites W3041807032 @default.
- W4225785140 cites W3102034102 @default.
- W4225785140 doi "https://doi.org/10.1161/circulationaha.120.051923" @default.
- W4225785140 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34672678" @default.
- W4225785140 hasPublicationYear "2021" @default.
- W4225785140 type Work @default.
- W4225785140 citedByCount "38" @default.
- W4225785140 countsByYear W42257851402021 @default.
- W4225785140 countsByYear W42257851402022 @default.
- W4225785140 countsByYear W42257851402023 @default.
- W4225785140 crossrefType "journal-article" @default.
- W4225785140 hasAuthorship W4225785140A5001520142 @default.
- W4225785140 hasAuthorship W4225785140A5011792926 @default.
- W4225785140 hasAuthorship W4225785140A5015739454 @default.
- W4225785140 hasAuthorship W4225785140A5022712399 @default.
- W4225785140 hasAuthorship W4225785140A5026182510 @default.
- W4225785140 hasAuthorship W4225785140A5035502859 @default.
- W4225785140 hasAuthorship W4225785140A5035620570 @default.
- W4225785140 hasAuthorship W4225785140A5045160257 @default.
- W4225785140 hasAuthorship W4225785140A5046337325 @default.
- W4225785140 hasAuthorship W4225785140A5048399752 @default.
- W4225785140 hasAuthorship W4225785140A5060151311 @default.
- W4225785140 hasAuthorship W4225785140A5061950827 @default.
- W4225785140 hasAuthorship W4225785140A5065018686 @default.
- W4225785140 hasAuthorship W4225785140A5065167900 @default.
- W4225785140 hasAuthorship W4225785140A5074434578 @default.
- W4225785140 hasAuthorship W4225785140A5076009391 @default.
- W4225785140 hasAuthorship W4225785140A5076082024 @default.
- W4225785140 hasAuthorship W4225785140A5080194664 @default.
- W4225785140 hasAuthorship W4225785140A5080691366 @default.
- W4225785140 hasAuthorship W4225785140A5081723201 @default.
- W4225785140 hasAuthorship W4225785140A5089998359 @default.
- W4225785140 hasAuthorship W4225785140A5090828942 @default.