| First Author | Ong FS | Year | 2012 |
| Journal | Hypertension | Volume | 59 |
| Issue | 2 | Pages | 283-90 |
| PubMed ID | 22203735 | Mgi Jnum | J:280036 |
| Mgi Id | MGI:6367861 | Doi | 10.1161/HYPERTENSIONAHA.111.180844 |
| Citation | Ong FS, et al. (2012) Increased angiotensin II-induced hypertension and inflammatory cytokines in mice lacking angiotensin-converting enzyme N domain activity. Hypertension 59(2):283-90 |
| abstractText | -Angiotensin-converting enzyme (ACE) is composed of the N- and C-terminal catalytic domains. To study the role of the ACE domains in the inflammatory response, N-knockout (KO) and C-KO mice, models lacking 1 of the 2 ACE domains, were analyzed during angiotensin II-induced hypertension. At 2 weeks, N-KO mice have systolic blood pressures that averaged 173+/-4.6 mm Hg, which is more than 25 mm Hg higher than the blood pressures observed in wild-type or C-KO mice (146+/-3.2 and 147+/-4.2 mm Hg). After 3 weeks, blood pressure differences between N-KO, C-KO, and wild-type were even more pronounced. Macrophages from N-KO mice have increased expression of tumor necrosis factor alpha after stimulation with either lipopolysaccharide (about 4-fold) or angiotensin II (about 2-fold), as compared with C-KO or wild-type mice. Inhibition of the enzyme prolyl oligopeptidase, responsible for the formation of acetyl-SerAspLysPro and other peptides, eliminated the blood pressure difference and the difference in tumor necrosis factor alpha expression between angiotensin II-treated N-KO and wild-type mice. However, this appears independent of acetyl-SerAspLysPro. These data establish significant differences in the inflammatory response as a function of ACE N- or C-domain catalytic activity. They also indicate a novel role of prolyl oligopeptidase in the cytokine regulation and in the blood pressure response to experimental hypertension. |
