AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia
| العنوان: | AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia |
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| المؤلفون: | Hui-Yu Bai, Hui Li, Xiang Zhou, Hai-Bo Gu, Bao-Shuai Shan |
| المصدر: | American Journal of Hypertension. 35:884-891 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Sirolimus, Sulfonamides, Angiotensin II, Myocytes, Smooth Muscle, Imidazoles, Thiophenes, Receptor, Angiotensin, Type 2, Muscle, Smooth, Vascular, Mice, Glucose, Superoxides, Hyperglycemia, Internal Medicine, Animals, Carrier Proteins, Cells, Cultured, Cellular Senescence |
| الوصف: | BACKGROUND Hyperglycemia has been widely reported to induce vascular senescence. We have previously demonstrated that angiotensin II (Ang II) could promote brain vascular smooth muscle cell (VSMC) senescence, and its type 2 (AT2) receptor deletion could enhance VSMC senescence. Therefore, we examined the possible cross-talk between Ang II and hyperglycemia on VSMC senescence, and the roles of AT2 receptor agonist, compound 21 (C21) on it. METHODS Aortic VSMCs were prepared from adult male mice and stimulated with Ang II and/or high glucose (Glu) and/or C21 and/or an autophagy inhibitor, 3-methyladenine (3-MA), and/or an autophagy agonist, rapamycin (RAP) for the indicated times. Cellular senescence, oxidative stress, and protein expressions were evaluated. RESULTS Combination treatment with Ang II and Glu synergistically increased the proportion of VSMC senescent area compared with control group and each treatment alone, which was almost completely attenuated by C21 treatment. Moreover, combination treatment induced significant changes in the levels of superoxide anion, the expressions of p21 and pRb, and the ratio of LC3B II/I expression, which were also significantly attenuated by C21 treatment. The proportion of VSMC senescent area and the levels of superoxide anion by combination treatment were increased after 3-MA treatment, and the proportion of senescent area and the expressions of p21 and pRb were decreased after RAP treatment, both of which were further attenuated by C21 treatment. CONCLUSIONS Ang II and hyperglycemia synergistically promoted VSMC senescence, at least partly through the participation by autophagy, oxidative stress, and p21-pRb pathway, which could be inhibited by C21. |
| تدمد: | 1941-7225 0895-7061 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6b0a4830e14d1b9f43ccb5da04dbb41Test https://doi.org/10.1093/ajh/hpac083Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....e6b0a4830e14d1b9f43ccb5da04dbb41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19417225 08957061 |
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