The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Novel Mechanism for Endothelial Dysfunction: Dysregulation of Dimethylarginine Dimethylaminohydrolase
Abstract
Background —Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Plasma levels of ADMA are elevated in individuals with hypercholesterolemia or atherosclerosis. We postulated that reduced degradation of ADMA may play a role in the accumulation of ADMA in these individuals. Accordingly, we studied the effects of oxidized LDL (oxLDL) or tumor necrosis factor-α (TNF-α) on the accumulation of ADMA by transformed human umbilical vein endothelial cells (ECV304) and on the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which degrades ADMA. Methods and Results —ECV304 were incubated with or without native LDL (100 μg/mL), oxLDL (100 μg/mL), or TNF-α (250 U/mL) for 48 hours. The concentration of ADMA in the conditioned medium was determined by high-performance liquid chromatography. Western blotting was performed to evaluate DDAH expression. We assayed DDAH activity by determining l -citrulline formation from ADMA. The addition of oxLDL or TNF-α to ECV304 significantly increased the level of ADMA in the conditioned medium. The effect of oxLDL or TNF-α was not due to a change in DDAH expression but rather to the reduction of DDAH activity. To determine whether dysregulation of DDAH also occurred in vivo, New Zealand White rabbits were fed normal chow or a high-cholesterol diet. Hypercholesterolemia significantly reduced aortic, renal, and hepatic DDAH activity. Conclusions —These results suggest that the endothelial vasodilator dysfunction observed in hypercholesterolemia may be due to reduced degradation of ADMA, the endogenous inhibitor of NOS.
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
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
Böger, R. H., Bode-Böger, S. M., Szuba, A., Tsao, P. S., Chan, J. R., Tangphao, O., Blaschke, T. F., & Cooke, J. P. (1998) · Circulation · doi:10.1161/01.cir.98.18.1842 · Cited by 1,181
Self-citationHigh-density lipoprotein inhibits the oxidative modification of low-density lipoprotein
Parthasarathy, S., Barnett, J., & Fong, L. G. (1990) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(90)90314-n · Cited by 827
Böger, R. H., Bode-Böger, S. M., Thiele, W., Junker, W., Alexander, K., & Frölich, J. C. (1997) · Circulation · doi:10.1161/01.cir.95.8.2068 · Cited by 490
Endogenous Dimethylarginine as an Inhibitor of Nitric Oxide Synthesis
Vallance, P., Leone, A., Calver, A., Collier, J., & Moncada, S. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199204002-00018 · Cited by 469
Long-term l -Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function in Humans
Lerman, A., Burnett, J. C., Higano, S. T., McKinley, L. J., & Holmes, D. R. (1998) · Circulation · doi:10.1161/01.cir.97.21.2123 · Cited by 426
Khripach, V. A., Zhabinskii, V. N., & de Groot, A. E. (1999) · Brassinosteroids · doi:10.1016/b978-012406360-0/50004-6 · Cited by 419
Kakimoto, Y., & Akazawa, S. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62716-4 · Cited by 407
Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase
MacAllister, R. J., Parry, H., Kimoto, M., Ogawa, T., Russell, R. J., Hodson, H., Whitley, G. S. J., & Vallance, P. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb16069.x · Cited by 393
Self-citationOgawa, T., Kimoto, M., & Sasaoka, K. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81786-0 · Cited by 360
Self-citation
Cited by
Zoccali, C., Bode-Böger, S. M., Mallamaci, F., Benedetto, F. A., Tripepi, G., Malatino, L. S., Cataliotti, A., Bellanuova, I., Fermo, I., Frölich, J. C., et al. (2001) · The Lancet · doi:10.1016/s0140-6736(01)07217-8 · Cited by 1,087
Achan, V., Broadhead, M., Malaki, M., Whitley, G., Leiper, J., MacAllister, R., & Vallance, P. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000081742.92006.59 · Cited by 593
Vallance, P., & Leiper, J. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000128897.54893.26 · Cited by 553
Diabetes Mellitus Enhances Vascular Matrix Metalloproteinase Activity: Role of Oxidative Stress
Uemura, S., Matsushita, H., Li, W., Glassford, A. J., Asagami, T., Lee, K.-H., Harrison, D. G., & Tsao, P. S. (2001) · Circulation Research · doi:10.1161/hh1201.092042 · Cited by 485
Self-citationRegulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells
Mann, G. E., Yudilevich, D. L., & Sobrevia, L. (2003) · Physiological Reviews · doi:10.1152/physrev.00022.2002 · Cited by 430
Metadata
- Authors
- Ito, A., Tsao, P. S., Adimoolam, S., Kimoto, M., Ogawa, T., & Cooke, J. P.
- Venue
- Circulation
- Published
- 1999-06-22
- Volume
- 99
- Issue
- 24
- Pages
- 3092-3095
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1970798352
- Cited by
- 631
- References
- 17
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- closed
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: Novel Mechanism for Endothelial Dysfunction: Dysregulation of Dimethylarginine Dimethylaminohydrolase. https://app.cochat.ai/papers/10.1161/01.cir.99.24.3092
- The paper
- Ito, A., Tsao, P. S., Adimoolam, S., Kimoto, M., Ogawa, T., & Cooke, J. P. (1999). Novel Mechanism for Endothelial Dysfunction: Dysregulation of Dimethylarginine Dimethylaminohydrolase. Circulation. https://doi.org/10.1161/01.cir.99.24.3092
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.
