The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Angiotensin II Mediates Angiotensin Converting Enzyme Type 2 Internalization and Degradation Through an Angiotensin II Type I Receptor–Dependent Mechanism
Open accessAbstract
Angiotensin-converting enzyme type 2 (ACE2) is a pivotal component of the renin–angiotensin system, promoting the conversion of angiotensin II (Ang-II) to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contributes to the development of Ang-II–mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 downregulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT 1 R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT 1 R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT 1 R transfection. Furthermore, coimmunoprecipitation experiments demonstrated that AT 1 R and ACE2 form complexes, and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT 2 or Mas receptors. In vivo, Ang-II–mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT 1 R-dependent mechanism.
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
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., et al. (2005) · Nature Medicine · doi:10.1038/nm1267 · Cited by 3,445
β-arrestin-mediated receptor trafficking and signal transduction
Shenoy, S. K., & Lefkowitz, R. J. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.05.002 · Cited by 712
Wang, H., Yang, P., Liu, K., Guo, F., Zhang, Y., Zhang, G., & Jiang, C. (2008) · Cell Research · doi:10.1038/cr.2008.15 · Cited by 707
Lambert, D. W., Yarski, M., Warner, F. J., Thornhill, P., Parkin, E. T., Smith, A. I., Hooper, N. M., & Turner, A. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505111200 · Cited by 694
The emerging role of ACE2 in physiology and disease
Hamming, I., Cooper, M., Haagmans, B., Hooper, N., Korstanje, R., Osterhaus, A., Timens, W., Turner, A., Navis, G., & van Goor, H. (2007) · The Journal of Pathology · doi:10.1002/path.2162 · Cited by 434
Atwood, B. K., Lopez, J., Wager-Miller, J., Mackie, K., & Straiker, A. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-14 · Cited by 424
Doobay, M. F., Talman, L. S., Obr, T. D., Tian, X., Davisson, R. L., & Lazartigues, E. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00292.2006 · Cited by 406
Self-citationInoue, Y., Tanaka, N., Tanaka, Y., Inoue, S., Morita, K., Zhuang, M., Hattori, T., & Sugamura, K. (2007) · Journal of Virology · doi:10.1128/jvi.00253-07 · Cited by 369
The discovery of angiotensin‐converting enzyme 2 and its role in acute lung injury in mice
Imai, Y., Kuba, K., & Penninger, J. M. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2007.040048 · Cited by 334
ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good
Xu, P., Sriramula, S., & Lazartigues, E. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00222.2010 · Cited by 283
Self-citation
Cited by
Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis
Trougakos, I. P., Terpos, E., Alexopoulos, H., Politou, M., Paraskevis, D., Scorilas, A., Kastritis, E., Andreakos, E., & Dimopoulos, M. A. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.04.007 · Cited by 273
p38 MAPK inhibition: A promising therapeutic approach for COVID-19
Grimes, J. M., & Grimes, K. V. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.05.007 · Cited by 259
Sarzani, R., Giulietti, F., Di Pentima, C., Giordano, P., & Spannella, F. (2020) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00189.2020 · Cited by 86
Potential mechanisms of hemorrhagic stroke in elderly COVID-19 patients
Wang, H., Tang, X., Fan, H., Luo, Y., Song, Y., Xu, Y., & Chen, Y. (2020) · Aging · doi:10.18632/aging.103335 · Cited by 69
Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
Rahmani, W., Chung, H., Sinha, S., Bui-Marinos, M. P., Arora, R., Jaffer, A., Corcoran, J. A., Biernaskie, J., & Chun, J. (2022) · iScience · doi:10.1016/j.isci.2022.103818 · Cited by 25
Metadata
- Authors
- Deshotels, M. R., Xia, H., Sriramula, S., Lazartigues, E., & Filipeanu, C. M.
- Venue
- Hypertension
- Published
- 2014-12
- Volume
- 64
- Issue
- 6
- Pages
- 1368-1375
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2104620139
- Cited by
- 264
- References
- 46
- FWCI
- 2.74
- 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: Angiotensin II Mediates Angiotensin Converting Enzyme Type 2 Internalization and Degradation Through an Angiotensin II Type I Receptor–Dependent Mechanism. https://app.cochat.ai/papers/10.1161/hypertensionaha.114.03743
- The paper
- Deshotels, M. R., Xia, H., Sriramula, S., Lazartigues, E., & Filipeanu, C. M. (2014). Angiotensin II Mediates Angiotensin Converting Enzyme Type 2 Internalization and Degradation Through an Angiotensin II Type I Receptor–Dependent Mechanism. Hypertension. https://doi.org/10.1161/hypertensionaha.114.03743
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.
