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| Item Type: | Article |
|---|---|
| Title: | Dual deficiency of angiotensin-converting enzyme-2 and Mas receptor enhances angiotensin II-induced hypertension and hypertensive nephropathy |
| Creators Name: | Ni, J. and Yang, F. and Huang, X.R. and Meng, J. and Chen, J. and Bader, M. and Penninger, J.M. and Fung, E. and Yu, X.Q. and Lan, H.Y. |
| Abstract: | Angiotensin-converting enzyme-2 (ACE2) and Mas receptor are the major components of the ACE2/Ang 1-7/Mas axis and have been shown to play a protective role in hypertension and hypertensive nephropathy individually. However, the effects of dual deficiency of ACE2 and Mas (ACE2/Mas) on Ang II-induced hypertensive nephropathy remain unexplored, which was investigated in this study in a mouse model of hypertension induced in either ACE2 knockout (KO) or Mas KO mice and in double ACE2/Mas KO mice by subcutaneously chronic infusion of Ang II. Compared with wild-type (WT) animals, mice lacking either ACE2 or Mas significantly increased blood pressure over 7-28 days following a chronic Ang II infusion (P < .001), which was further exacerbated in double ACE2/Mas KO mice (P < .001). Furthermore, compared to a single ACE2 or Mas KO mice, mice lacking ACE2/Mas developed more severe renal injury including higher levels of serum creatinine and a further reduction in creatinine clearance, and progressive renal inflammation and fibrosis. Mechanistically, worsen hypertensive nephropathy in double ACE2/Mas KO mice was associated with markedly enhanced AT1-ERK1/2-Smad3 and NF-κB signalling, thereby promoting renal fibrosis and renal inflammation in the hypertensive kidney. In conclusion, ACE2 and Mas play an additive protective role in Ang II-induced hypertension and hypertensive nephropathy. Thus, restoring the ACE2/Ang1-7/Mas axis may represent a novel therapy for hypertension and hypertensive nephropathy. |
| Keywords: | ACE2, Ang II, Hypertension, Hypertensive Nephropathy, Mas, NF‐κB, TGF‐β/Smad3, Animals, Mice |
| Source: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| Publisher: | Wiley |
| Volume: | 24 |
| Number: | 22 |
| Page Range: | 13093-13103 |
| Date: | November 2020 |
| Official Publication: | https://doi.org/10.1111/jcmm.15914 |
| PubMed: | View item in PubMed |
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