Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy.
Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important member of the renin angiotensin system. Previously, we observed that central ACE2 reduces the development of hypertension following chronic angiotensin II (Ang-II) infusion in syn-hACE2 transgenic (SA) mice, in which the h...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3498357?pdf=render |
| _version_ | 1818141208572067840 |
|---|---|
| author | Yumei Feng Chetan Hans Elizabeth McIlwain Kurt J Varner Eric Lazartigues |
| author_facet | Yumei Feng Chetan Hans Elizabeth McIlwain Kurt J Varner Eric Lazartigues |
| author_sort | Yumei Feng |
| collection | DOAJ |
| description | Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important member of the renin angiotensin system. Previously, we observed that central ACE2 reduces the development of hypertension following chronic angiotensin II (Ang-II) infusion in syn-hACE2 transgenic (SA) mice, in which the human ACE2 transgene is selectively targeted to neurons. To study the physiological consequences of central ACE2 over-expression on cardiac function and cardiac hypertrophy, SA and non-transgenic (NT) mice were infused with Ang-II (600 ng/kg/min, sc) for 14 days, and cardiac function was assessed by echocardiography. Blood pressure (BP), hemodynamic parameters, left ventricle (LV) mass/tibia length, relative ventricle wall thickness (2PW/LVD), cardiomyocyte diameters and collagen deposition were similar (P>0.05) between NT and SA mice during saline infusion. After a 2-week infusion, BP was elevated in NT but not in SA mice. Although ejection fraction and fractional shortening were not altered, Ang-II infusion increased 2PW/LVD compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV mass/tibia ratios were significantly lower in SA compared to NT mice at the end of infusion. Moreover, Ang-II infusion significantly increased arterial collagen deposition and cardiomyocytes diameter in NT mice but not in transgenic animals (P<0.05). More importantly, ACE2 over expression significantly reduced the Ang-II-mediated increase in urine norepinephrine levels in SA compared to NT mice. The protective effect of ACE2 appears to involve reductions in Ang-II-mediated hypertension and sympathetic nerve activity. |
| first_indexed | 2024-12-11T10:56:14Z |
| format | Article |
| id | doaj.art-f80886bd6a124157a70bf2e0ed6229b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:56:14Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f80886bd6a124157a70bf2e0ed6229b32022-12-22T01:10:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4891010.1371/journal.pone.0048910Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy.Yumei FengChetan HansElizabeth McIlwainKurt J VarnerEric LazartiguesAngiotensin-converting enzyme type 2 (ACE2) has been shown to be an important member of the renin angiotensin system. Previously, we observed that central ACE2 reduces the development of hypertension following chronic angiotensin II (Ang-II) infusion in syn-hACE2 transgenic (SA) mice, in which the human ACE2 transgene is selectively targeted to neurons. To study the physiological consequences of central ACE2 over-expression on cardiac function and cardiac hypertrophy, SA and non-transgenic (NT) mice were infused with Ang-II (600 ng/kg/min, sc) for 14 days, and cardiac function was assessed by echocardiography. Blood pressure (BP), hemodynamic parameters, left ventricle (LV) mass/tibia length, relative ventricle wall thickness (2PW/LVD), cardiomyocyte diameters and collagen deposition were similar (P>0.05) between NT and SA mice during saline infusion. After a 2-week infusion, BP was elevated in NT but not in SA mice. Although ejection fraction and fractional shortening were not altered, Ang-II infusion increased 2PW/LVD compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV mass/tibia ratios were significantly lower in SA compared to NT mice at the end of infusion. Moreover, Ang-II infusion significantly increased arterial collagen deposition and cardiomyocytes diameter in NT mice but not in transgenic animals (P<0.05). More importantly, ACE2 over expression significantly reduced the Ang-II-mediated increase in urine norepinephrine levels in SA compared to NT mice. The protective effect of ACE2 appears to involve reductions in Ang-II-mediated hypertension and sympathetic nerve activity.http://europepmc.org/articles/PMC3498357?pdf=render |
| spellingShingle | Yumei Feng Chetan Hans Elizabeth McIlwain Kurt J Varner Eric Lazartigues Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. PLoS ONE |
| title | Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. |
| title_full | Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. |
| title_fullStr | Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. |
| title_full_unstemmed | Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. |
| title_short | Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy. |
| title_sort | angiotensin converting enzyme 2 over expression in the central nervous system reduces angiotensin ii mediated cardiac hypertrophy |
| url | http://europepmc.org/articles/PMC3498357?pdf=render |
| work_keys_str_mv | AT yumeifeng angiotensinconvertingenzyme2overexpressioninthecentralnervoussystemreducesangiotensiniimediatedcardiachypertrophy AT chetanhans angiotensinconvertingenzyme2overexpressioninthecentralnervoussystemreducesangiotensiniimediatedcardiachypertrophy AT elizabethmcilwain angiotensinconvertingenzyme2overexpressioninthecentralnervoussystemreducesangiotensiniimediatedcardiachypertrophy AT kurtjvarner angiotensinconvertingenzyme2overexpressioninthecentralnervoussystemreducesangiotensiniimediatedcardiachypertrophy AT ericlazartigues angiotensinconvertingenzyme2overexpressioninthecentralnervoussystemreducesangiotensiniimediatedcardiachypertrophy |