The overexpression of twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice
Open accessAbstract
Myocardial mitochondrial DNA (mtDNA) copy number decreases in heart failure. In post-myocardial infarction mice, increasing mtDNA copy number by overexpressing mitochondrial transcription factor attenuates mtDNA deficiency and ameliorates pathological remodeling thereby markedly improving survival. However, the functional significance of increased mtDNA copy number in hypertensive heart disease remains unknown. We addressed this question using transgenic mice that overexpress Twinkle helicase (Twinkle; Tg), the mtDNA helicase, and examined whether Twinkle overexpression protects the heart from left ventricular (LV) remodeling and failure after pressure overload created by transverse aortic constriction (TAC). Twinkle overexpression increased mtDNA copy number by 2.2 ± 0.1-fold. Heart weight, LV diastolic volume and wall thickness were comparable between Tg and wild type littermates (WT) at 28 days after TAC operation. LV end-diastolic pressure increased in WT after TAC (8.6 ± 2.8 mmHg), and this increase was attenuated in Tg (4.6 ± 2.6 mmHg). Impaired LV fractional shortening after TAC operation was also suppressed in Tg, as measured by echocardiography (WT: 16.2 ± 7.2% vs Tg: 20.7 ± 6.2%). These LV functional improvements were accompanied by a decrease in interstitial fibrosis (WT: 10.6 ± 1.1% vs Tg: 3.0 ± 0.6%). In in vitro studies, overexpressing Twinkle using an adenovirus vector in cultured cardiac fibroblasts significantly suppressed mRNA of collagen 1a, collagen 3a and connective tissue growth factor, and angiotensin II-induced transforming growth factor β1 expression. The findings suggest that Twinkle overexpression prevents LV function deterioration. In conclusion, Twinkle overexpression increases mtDNA copy number and ameliorates the progression of LV fibrosis and heart failure in a mouse pressure overload model. Increasing mtDNA copy number by Twinkle overexpression could be a novel therapeutic strategy for hypertensive heart disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mice overexpressing Twinkle are protected from left ventricular remodeling in the heart.
“Mice overexpressing Twinkle are protected from left ventricular remodeling in the heart (Tanaka et al., 2013).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Tanaka et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Global burden of hypertension: analysis of worldwide data
Kearney, P. M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P. K., & He, J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)17741-1 · Cited by 8,578 · see citing works
Heart Disease and Stroke Statistics—2012 Update: A Report From the American Heart Association
Writing Group Members, Roger, V. L., Go, A. S., Lloyd-Jones, D. M., Benjamin, E. J., Berry, J. D., Borden, W. B., Bravata, D. M., Dai, S., Ford, E. S., et al. (2012) · Circulation · doi:10.1161/cir.0b013e31823ac046 · Cited by 7,333 · see citing works
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Global burden of hypertension: analysis of worldwide data
(2005) · doi:10.1016/s0140-6736(05)70151-3 · Cited by 3,289 · see citing works
Heidenreich, P. A., Trogdon, J. G., Khavjou, O. A., Butler, J., Dracup, K., Ezekowitz, M. D., Finkelstein, E. A., Hong, Y., Johnston, S. C., Khera, A., et al. (2011) · Circulation · doi:10.1161/cir.0b013e31820a55f5 · Cited by 3,208 · see citing works
Biernacka, A., Dobaczewski, M. P., & Frangogiannis, N. G. (2011) · Growth Factors · doi:10.3109/08977194.2011.595714 · Cited by 1,175 · see citing works
Transforming growth factor (TGF)-β signaling in cardiac remodeling
Dobaczewski, M. P., Chen, W., & Frangogiannis, N. G. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.10.033 · Cited by 933 · see citing works
Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy
Takimoto, E., Champion, H. C., Li, M., Belardi, D. F., Ren, S. V., Rodríguez, E. R., Bedja, D., Gabrielson, K. L., Wang, Y., & Kass, D. A. (2005) · Nature Medicine · doi:10.1038/nm1175 · Cited by 902 · see citing works
Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., et al. (2001) · Nature Genetics · doi:10.1038/90058 · Cited by 882 · see citing works
NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart
Kuroda, J., Ago, T., Matsushima, S., Zhai, P., Schneider, M. D., & Sadoshima, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002178107 · Cited by 772 · see citing works
Ide, T., Tsutsui, H., Hayashidani, S., Kang, D., Suematsu, N., Nakamura, K., Utsumi, H., Hamasaki, N., & Takeshita, A. (2001) · Circulation Research · doi:10.1161/01.res.88.5.529 · Cited by 733 · see citing works
Self-citationDı́ez, J., Querejeta, R., López, B., González, A., Larman, M., & Ubago, J. L. M. (2002) · Circulation · doi:10.1161/01.cir.0000017264.66561.3d · Cited by 636 · see citing works
Tyynismaa, H., Mjosund, K. P., Wanrooij, S., Lappalainen, I., Ylikallio, E., Jalanko, A., Spelbrink, J. N., Paetau, A., & Suomalainen, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505551102 · Cited by 342 · see citing works
Efficient Construction of a Recombinant Adenovirus Vector by an Improved In Vitro Ligation Method
Mizuguchi, H., & Kay, M. A. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.17-2577 · Cited by 338 · see citing works
Korhonen, J. A., Gaspari, M., & Falkenberg, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306981200 · Cited by 298 · see citing works
Ikeuchi, M., Matsusaka, H., Kang, D., Matsushima, S., Ide, T., Kubota, T., Fujiwara, T., Hamasaki, N., Takeshita, A., Sunagawa, K., et al. (2005) · Circulation · doi:10.1161/circulationaha.104.524835 · Cited by 273 · see citing works
Self-citationMatsushima, S., Ide, T., Yamato, M., Matsusaka, H., Hattori, F., Ikeuchi, M., Kubota, T., Sunagawa, K., Hasegawa, Y., Kurihara, T., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.582239 · Cited by 262 · see citing works
Self-citationDefective DNA Replication Impairs Mitochondrial Biogenesis In Human Failing Hearts
Karamanlidis, G., Nascimben, L., Couper, G. S., Shekar, P., del Monte, F., & Tian, R. (2010) · Circulation Research · doi:10.1161/circresaha.109.212753 · Cited by 258 · see citing works
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number
Tyynismaa, H., Sembongi, H., Bokori-Brown, M., Granycome, C., Ashley, N., Poulton, J., Jalanko, A., Spelbrink, J. N., Holt, I. J., & Suomalainen, A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh342 · Cited by 250 · see citing works
Lanza, I. R., Zabielski, P., Klaus, K. A., Morse, D. M., Heppelmann, C. J., Bergen, H. R., Dasari, S., Walrand, S., Short, K. R., Johnson, M. L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.003 · Cited by 227 · see citing works
New Targets to Treat the Structural Remodeling of the Myocardium
González, A., Ravassa, S., Beaumont, J., López, B., & Dı́ez, J. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.06.058 · Cited by 176 · see citing works
Matsusaka, H., Ide, T., Matsushima, S., Ikeuchi, M., Kubota, T., Sunagawa, K., Kinugawa, S., & Tsutsui, H. (2006) · Hypertension · doi:10.1161/01.hyp.0000208840.30778.00 · Cited by 159 · see citing works
Self-citationAntonická, H., Sasarman, F., Kennaway, N. G., & Shoubridge, E. A. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl106 · Cited by 140 · see citing works
High mitochondrial DNA copy number has detrimental effects in mice
Ylikallio, E., Tyynismaa, H., Tsutsui, H., Ide, T., & Suomalainen, A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq163 · Cited by 137 · see citing works
Self-citationFujii, T., Onohara, N., Maruyama, Y., Tanabe, S., Kobayashi, H., Fukutomi, M., Nagamatsu, Y., Nishihara, N., Inoue, R., Sumimoto, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409397200 · Cited by 89 · see citing works
Lyly, A., Marjavaara, S. K., Kyttälä, A., Uusi-Rauva, K., Luiro, K., Kopra, O., Martinez, L. O., Tanhuanpää, K., Kalkkinen, N., Suomalainen, A., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn028 · Cited by 67 · see citing works
Self-citationGuo, W., Wong, S., Li, M., Liang, W., Liesa, M., Serra, C., Jasuja, R., Bartke, A., Kirkland, J. L., Shirihai, O., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051180 · Cited by 59 · see citing works
Fujino, T., Ide, T., Yoshida, M., Onitsuka, K., Tanaka, A., Hata, Y., Nishida, M., Takehara, T., Kanemaru, T., Kitajima, N., et al. (2012) · Mitochondrion · doi:10.1016/j.mito.2012.06.002 · Cited by 37 · see citing works
Self-citationHypertensive heart disease and fibrosis
Moncrieff, J., Lindsay, M. M., & Dunn, F. G. (2004) · Current Opinion in Cardiology · doi:10.1097/01.hco.0000127134.66225.97 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
Ikeda, M., Ide, T., Fujino, T., Arai, S., Saku, K., Kakino, T., Tyynismaa, H., Yamasaki, T., Yamada, K.-I., Kang, D., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119687 · Cited by 152 · see citing works
Self-citationPohjoismäki, J. L. O., Williams, S. L., Boettger, T., Goffart, S., Kim, J., Suomalainen, A., Moraes, C. T., & Braun, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303046110 · Cited by 45 · see citing works
Self-citation
- Authors
- Tanaka, A., Ide, T., Fujino, T., Onitsuka, K., Ikeda, M., Takehara, T., Hata, Y., Ylikallio, E., Tyynismaa, H., Suomalainen, A., & Sunagawa, K.
- Affiliations
- Kyushu University (JP)
- University of Helsinki (FI)
- Corresponding author
- Ide, Tomomi
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-06-28
- Volume
- 8
- Issue
- 6
- Pages
- e67642
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3695923
- OpenAlex
- W1990210494
- Cited by
- 23
- References
- 29
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 5 · 2021: 1 · 2020: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2013: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (23220013, 23591084)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- Twinkle helicase, mitochondrial DNA copy number, myocardial fibrosis, heart failure, pressure overload, transverse aortic constriction, hypertensive heart disease, left ventricular remodeling, interstitial fibrosis, cardiac fibroblasts, collagen expression, angiotensin II, TGF-β1, connective tissue growth factor, adenoviral gene transfer
- MeSH terms
- Animals, Aorta, Constriction, Disease Models, Animal, DNA Helicases, Echocardiography, Fibrosis, Heart, Heart Failure, Male, Mice, Transgenic, Pressure, Gene Expression, Ventricular Function, Left, Hypertrophy, Left Ventricular, Disease Progression, Ventricular Remodeling, Mitochondrial Proteins, Mice, DNA Copy Number Variations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
