Increased Angiotensin II–Induced Hypertension and Inflammatory Cytokines in Mice Lacking Angiotensin-Converting Enzyme N Domain Activity
—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,...
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Published in | Hypertension (Dallas, Tex. 1979) Vol. 59; no. 2; pp. 283 - 290 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hagerstown, MD
American Heart Association, Inc
01.02.2012
Lippincott Williams & Wilkins |
Subjects | |
Online Access | Get full text |
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Summary: | —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 α 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 α 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. |
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Bibliography: | Current address: Department of Immunology, Institute of Biotechnology, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, 350003, China denotes equal corresponding authorship |
ISSN: | 0194-911X 1524-4563 |
DOI: | 10.1161/HYPERTENSIONAHA.111.180844 |