The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure
Abstract
Background—: Atrial tissue fibrosis is often an important component of the atrial fibrillation (AF) substrate. Small noncoding microRNAs are important mediators in many cardiac remodeling paradigms. MicroRNA-21 (miR-21) has been suggested to be important in ventricular fibrotic remodeling by downregulating Sprouty-1, a protein that suppresses fibroblast proliferation. The present study examined the potential role of miR-21 in the atrial AF substrate resulting from experimental heart failure after myocardial infarction (MI). Methods and Results—: Large MIs (based on echocardiographic left ventricular wall motion score index) were created by left anterior descending coronary artery ligation in rats. Changes induced by MI versus sham controls were first characterized with echocardiography, histology, biochemistry, and in vivo electrophysiology. Additional MI rats were then randomized to receive anti–miR-21 (KD21) or scrambled control sequence (Scr21) injections into the left atrial myocardium. Progressive left ventricular enlargement, hypocontractility, left atrial dilation, fibrosis, refractoriness prolongation, and AF promotion occurred in MI rats versus sham controls. Atrial tissues of MI rats showed upregulation of miR-21, along with dysregulation of the target genes Sprouty-1, collagen-1, and collagen-3. KD21 treatment reduced atrial miR-21 expression levels in MI rats to values in sham rats, decreased AF duration from 417 (69–1595; median [Q1–Q3]) seconds to 3 (2–16) seconds (8 weeks after MI; P <0.05), and reduced atrial fibrous tissue content from 14.4±1.8% (mean±SEM) to 4.9±1.2% (8 weeks after MI; P <0.05) versus Scr21 controls. Conclusions—: MI-induced heart failure leads to AF-promoting atrial remodeling in rats. Atrial miR-21 knockdown suppresses atrial fibrosis and AF promotion, implicating miR-21 as an important signaling molecule for the AF substrate and pointing to miR-21 as a potential target for molecular interventions designed to prevent AF.
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Fuster, V., Rydén, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.177292 · Cited by 2,805
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., et al. (2008) · Nature · doi:10.1038/nature07511 · Cited by 2,349
Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications
Nattel, S., Burstein, B., & Dobrev, D. (2008) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.107.754564 · Cited by 1,124
Self-citationmiR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis
Liu, G., Friggeri, A., Yang, Y., Milosevic, J., Ding, Q., Thannickal, V. J., Kaminski, N., & Abraham, E. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100035 · Cited by 935
Wattigney, W. A., Mensah, G. A., & Croft, J. B. (2003) · Circulation · doi:10.1161/01.cir.0000083722.42033.0a · Cited by 505
Cited by
Atrial Remodeling and Atrial Fibrillation
Nattel, S., & Harada, M. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.02.555 · Cited by 736
Self-citationHeijman, J., Voigt, N., Nattel, S., & Dobrev, D. (2014) · Circulation Research · doi:10.1161/circresaha.114.302226 · Cited by 677
Self-citationEarly management of atrial fibrillation to prevent cardiovascular complications
Nattel, S., Guasch, E., Savelieva, I., Cosio, F. G., Valverde, I., Halperin, J. L., Conroy, J. M., Al-Khatib, S. M., Hess, P. L., Kirchhof, P., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu028 · Cited by 273
Self-citationMcManus, D. D., Tanriverdi, K., Lin, H., Esa, N., Kinno, M., Mandapati, D., Tam, S., Okike, O. N., Ellinor, P. T., Keaney, J. F., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2014.09.050 · Cited by 116
Potential Clinical Implications of miR-1 and miR-21 in Heart Disease and Cardioprotection
Kura, B., Kalocayova, B., Devaux, Y., & Bartekova, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030700 · Cited by 106
Metadata
- Authors
- Cardin, S., Guasch, E., Luo, X., Naud, P., Le Quang, K., Shi, Y., Tardif, J.-C., Comtois, P., & Nattel, S.
- Venue
- Circulation: Arrhythmia and Electrophysiology
- Published
- 2012-10
- Volume
- 5
- Issue
- 5
- Pages
- 1027-1035
- ISSN
- 1941-3084 (ISSN-L)
- 1941-3149
- OpenAlex
- W2140694824
- Cited by
- 189
- References
- 5
- FWCI
- 11.13
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure. https://app.cochat.ai/papers/10.1161/circep.112.973214
- The paper
- Cardin, S., Guasch, E., Luo, X., Naud, P., Le Quang, K., Shi, Y., Tardif, J.-C., Comtois, P., & Nattel, S. (2012). Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure. Circulation: Arrhythmia and Electrophysiology. https://doi.org/10.1161/circep.112.973214
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