Homocysteine up-regulates ET B receptors via suppression of autophagy in vascular smooth muscle cells
Abstract
The change of autophagy is implicated in cardiovascular diseases (CVDs). Homocysteine (Hcy) up-regulates endothelin type B (ET B) receptors in vascular smooth muscle cells (VSMCs). However, it is unclear whether autophagy is involved in Hcy-induced-up-regulation of ET B receptors in VSMCs. The present study was designed to examine the hypothesis that Hcy up-regulates ET B receptors by inhibiting autophagy in VSMCs. Hcy treated the rat superior mesenteric artery (SMA) without endothelium in the presence and absence of AICAR, rapamycin or MHY1485 for 24 h. The contractile responses to sarafotoxin 6c (S6c) (an ET B receptor agonist) were studied using a sensitive myograph. Levels of protein expression were determined using Western blot analysis. Punctate staining of LC3B was exanimated by immunofluorescence using confocal microscopy. The results showed that Hcy inhibited AMPK, and activated mTOR, followed by impairing autophagy, and increased the levels of ET B receptor protein expression and the ET B receptor-mediated contractile responses to S6c in SMA without endothelium. However, these effects were reversed by AICAR or rapamycin. Additionally, MHY1485 up-regulated the AICAR-inhibited ET B receptor-mediated contractile response and the levels of ET B receptor protein expression in presence of Hcy. In conclusion, this suggested that Hcy up-regulated ET B receptors by inhibiting autophagy in VSMCs via AMPK/mTOR signaling pathway.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
ETB and AT1 are involved in AMPK pathway by binding to their receptors.
“ETB and AT1 are reportedly involved in AMPK pathway by binding to their receptors [194,195].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [195]
Cites
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,467 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Self-citationAutophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116 · see citing works
Bolster, D. R., Crozier, S. J., Kimball, S. R., & Jefferson, L. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200171200 · Cited by 851 · see citing works
Mammalian AMP-activated protein kinase subfamily
Stapleton, D., Mitchelhill, K. I., Gao, G., Widmer, J., Michell, B. J., Teh, T., House, C. M., Fernandez, C. S., Cox, T., Witters, L. A., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.611 · Cited by 652 · see citing works
Autophagy in Human Health and Disease
Doria, A., Gatto, M., & Punzi, L. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1303158 · Cited by 621 · see citing works
AMPK–SKP2–CARM1 signalling cascade in transcriptional regulation of autophagy
Shin, H. R., Kim, H.-K., Oh, S., Lee, J.-G., Kee, M., Ko, H., Kweon, M., Won, K., & Baek, S. H. (2016) · Nature · doi:10.1038/nature18014 · Cited by 441 · see citing works
Martinet, W., & Meyer, G. R. Y. D. (2009) · Circulation Research · doi:10.1161/circresaha.108.188318 · Cited by 384 · see citing works
Long, L., Yang, X., Southwood, M. R., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300483 · Cited by 285 · see citing works
He, H., Dang, Y., Dai, F., Guo, Z., Wu, J., She, X., Pei, Y., Chen, Y., Ling, W., Wu, C., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303800200 · Cited by 273 · see citing works
Self-citationGrootaert, M. O., da Costa Martins, P. A., Bitsch, N., Pintelon, I., De Meyer, G. R., Martinet, W., & Schrijvers, D. M. (2015) · Autophagy · doi:10.1080/15548627.2015.1096485 · Cited by 267 · see citing works
Translational evidence that impaired autophagy contributes to arterial ageing
LaRocca, T. J., Henson, G. D., Thorburn, A. M., Sindler, A. L., Pierce, G. L., & Seals, D. R. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.229690 · Cited by 255 · see citing works
Molecular Organization of Target of Rapamycin Complex 2
Wullschleger, S., Loewith, R., Oppliger, W., & Hall, M. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505553200 · Cited by 231 · see citing works
AMPK regulates autophagy by phosphorylating BECN1 at threonine 388
Zhang, D., Wang, W., Sun, X., Xu, D., Wang, C., Zhang, Q., Wang, H., Luo, W., Chen, Y., Chen, H., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1185576 · Cited by 211 · see citing works
Self-citationRole of endothelin in cardiovascular disease
Agapitov, A. V., & Haynes, W. G. (2002) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.3317/jraas.2002.001 · Cited by 187 · see citing works
Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis
Brünner, F., Brás‐Silva, C., Cerdeira, A. S., & Leite-Moreira, A. F. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.11.001 · Cited by 181 · see citing works
Iwasa, S., Fan, J., Shimokama, T., Nagata, M., & Watanabe, T. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00134-3 · Cited by 107 · see citing works
Vikman, P. J., Beg, S., Khurana, T., et al. (2006) · Journal of neurosurgery · doi:10.3171/jns.2006.105.3.438 · Cited by 91 · see citing works
Autophagic regulation of smooth muscle cell biology
Salabei, J. K., & Hill, B. G. (2014) · Redox Biology · doi:10.1016/j.redox.2014.12.007 · Cited by 86 · see citing works
Tripathi, M., Zhang, C. W., Singh, B. K., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.374 · Cited by 81 · see citing works
Ischemic heart disease induce upregulation of endothelin receptor mRNA in human coronary arteries
Wackenfors, A., Emilson, M., Ingemansson, R., et al. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.11.001 · Cited by 67 · see citing works
Kelland, N. F., Kuc, R. E., McLean, D. L., et al. (2010) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y10-041 · Cited by 66 · see citing works
Dimitrijevic, I., Edvinsson, M.-L., Chen, Q., et al. (2009) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-9-40 · Cited by 39 · see citing works
Homocysteine reduces protein S-nitrosylation in endothelium
Chen, Y., Zhao, S., Wang, Y., Li, Y., Bai, L., Liu, R., Fan, J., & Liu, E. (2014) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2014.1920 · Cited by 33 · see citing works
Self-citationChen, Y., Liu, H., Zhang, H., Liu, E., Xu, C., & Su, X. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.11.011 · Cited by 33 · see citing works
Self-citationPan, H., Zhong, X., & Lee, S. (2016) · BMC Biochemistry · doi:10.1186/s12858-016-0069-6 · Cited by 27 · see citing works
Nilsson, D., Wackenfors, A., Gustafsson, L., et al. (2007) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002317 · Cited by 24 · see citing works
Homocysteine regulates endothelin type B receptors in vascular smooth muscle cells.
Chen, Y., Zhang, H.-M., Liu, E.-Q., Xu, C.-B., & Zhang, Y.-P. (2016) · Vascular pharmacology · doi:10.1016/j.vph.2016.08.011 · Cited by 23 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Wei, M., Gan, L., Liu, Z., Liu, L., Chang, J.-R., Yin, D.-C., Cao, H.-L., Su, X.-L., & Smith, W. W. (2020) · Cardiorenal Medicine · doi:10.1159/000503224 · Cited by 52 · see citing works
Self-citation
- Authors
- Chen, Y., Zhang, H., Liu, H., Li, K., & Su, X.
- Affiliations
- Xi'an Medical University (CN)
- Corresponding author
- Chen, Yulong
- Su, Xingli
- Venue
- Microvascular Research
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 119
- Pages
- 13-21
- ISSN
- 0026-2862 (ISSN-L)
- OpenAlex
- W2794471811
- Cited by
- 19
- References
- 30
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 5
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microvascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81500350)
- Supporting Fund Project of Xi'an Medical University (2016PT27)
- Education Department of Shaanxi Province (16JS098)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- homocysteine, endothelin B receptor, autophagy, vascular smooth muscle cells, AMPK/mTOR signaling, MHY1485, AICAR, rapamycin, sarafotoxin S6c, vascular contractility, LC3B, cardiovascular disease
- MeSH terms
- Animals, Autophagy, Homocysteine, Humans, Muscle, Smooth, Vascular, Vasoconstriction, Signal Transduction, Up-Regulation, Rats, Sprague-Dawley, Mesenteric Artery, Superior, Myocytes, Smooth Muscle, Receptor, Endothelin B, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases, In Vitro Techniques
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