The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
Open accessAbstract
Loss of cardiac myocytes in heart failure is thought to occur largely through an apoptotic process. Here we show that heart failure can also be precipitated through myocyte necrosis associated with Ca2+ overload. Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel (LTCC) activity showed progressive myocyte necrosis that led to pump dysfunction and premature death, effects that were dramatically enhanced by acute stimulation of beta-adrenergic receptors. Enhanced Ca2+ influx-induced cellular necrosis and cardiomyopathy was prevented with either LTCC blockers or beta-adrenergic receptor antagonists, demonstrating a proximal relationship among beta-adrenergic receptor function, Ca2+ handling, and heart failure progression through necrotic cell loss. Mechanistically, loss of cyclophilin D, a regulator of the mitochondrial permeability transition pore that underpins necrosis, blocked Ca2+ influx-induced necrosis of myocytes, heart failure, and isoproterenol-induced premature death. In contrast, overexpression of the antiapoptotic factor Bcl-2 was ineffective in mitigating heart failure and death associated with excess Ca2+ influx and acute beta-adrenergic receptor stimulation. This paradigm of mitochondrial- and necrosis-dependent heart failure was also observed in other mouse models of disease, which supports the concept that heart failure is a pleiotropic disorder that involves not only apoptosis, but also necrotic loss of myocytes in association with dysregulated Ca2+ handling and beta-adrenergic receptor signaling.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280
Self-citationLong-term trends in the incidence of and survival with heart failure
Levy, D., Kenchaiah, S., Larson, M. G., Benjamin, E. J., Kupka, M. J., Ho, K. K. L., Murabito, J. M., & Vasan, R. S. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020265 · Cited by 2,152
Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., & Tsujimoto, Y. (2005) · Nature · doi:10.1038/nature03317 · Cited by 1,635
A mechanistic role for cardiac myocyte apoptosis in heart failure
Wencker, D., Chandra, M., Nguyen, K., Miao, W., Garantziotis, S., Factor, S. M., Shirani, J., Armstrong, R. C., & Kitsis, R. N. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17664 · Cited by 765
Oudit, G. Y., Sun, H., Trivieri, M. G., Koch, S. E., Dawood, F., Ackerley, C., Yazdanpanah, M., Wilson, G. J., Schwartz, A., Liu, P. P., et al. (2003) · Nature Medicine · doi:10.1038/nm920 · Cited by 480
The enhanced contractility of the phospholamban-deficient mouse heart persists with aging
Slack, J. P., Grupp, I. L., Dash, R., Holder, D., Schmidt, A., Gerst, M. J., Tamura, T., Tilgmann, C., James, P. F., Johnson, R., et al. (2001) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2001.1370 · Cited by 64
Cited by
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Del Re, D. P., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 961
CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis
Zhang, T., Zhang, Y., Cui, M., Jin, L., Wang, Y., Lv, F., Liu, Y., Zheng, W., Shang, H., Zhang, J., et al. (2016) · Nature Medicine · doi:10.1038/nm.4017 · Cited by 790
Self-citationCell Death in the Pathogenesis of Heart Disease: Mechanisms and Significance
Whelan, R. S., Kaplinskiy, V., & Kitsis, R. N. (2010) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163111 · Cited by 759
Tackling heart failure in the twenty-first century
Mudd, J. O., & Kass, D. A. (2008) · Nature · doi:10.1038/nature06798 · Cited by 406
The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability
Luongo, T. S., Lambert, J. P., Gross, P., Nwokedi, M., Lombardi, A. A., Shanmughapriya, S., Carpenter, A. C., Kolmetzky, D., Gao, E., van Berlo, J. H., et al. (2017) · Nature · doi:10.1038/nature22082 · Cited by 396
Self-citation
Metadata
- Authors
- Nakayama, H., Chen, X., Baines, C. P., Klevitsky, R., Zhang, X., Zhang, H., Jaleel, N., Chua, B. H. L., Hewett, T. E., Robbins, J., Houser, S. R., & Molkentin, J. D.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-09-04
- Volume
- 117
- Issue
- 9
- Pages
- 2431-2444
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2109686719
- Cited by
- 405
- References
- 7
- FWCI
- 22.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. https://app.cochat.ai/papers/10.1172/jci31060
- The paper
- Nakayama, H., Chen, X., Baines, C. P., Klevitsky, R., Zhang, X., Zhang, H., Jaleel, N., Chua, B. H. L., Hewett, T. E., Robbins, J., Houser, S. R., & Molkentin, J. D. (2007). Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. Journal of Clinical Investigation. https://doi.org/10.1172/jci31060
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
