PMID- 22613639
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20201209
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 125
IP  - 8
DP  - 2012 Apr
TI  - Angiotensin-converting enzyme 2 activation protects against pulmonary arterial 
      hypertension through improving early endothelial function and mediating cytokines 
      levels.
PG  - 1381-8
AB  - BACKGROUND: Increasing evidences indicate that an activated renin-angiotensin 
      system (RAS) causes an imbalance between the vasoconstrictive and vasodilator 
      mechanisms involving the pulmonary circulation leading to the development of 
      pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a 
      primary component of the vasoprotective axis in RAS, is recently identified that 
      it has regulatory actions in lung pathophysiology, but the mechanism in these 
      processes is uncertain yet. METHODS: Severe PAH was induced by monocrotaline 
      injection one week following pneumonectomy in rats. The activation of ACE2 by 
      continuous injection of resorcinolnaphthalein was studied by real time-polymerase 
      chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. 
      Endothelial functions were evaluated by the response to acetylcholine and 
      cytokines were measured by RT-PCR seven days after monocrotaline injection. The 
      PAH-related hemodynamics and pathological changes were examined at day 21 when 
      severe PAH was completely established. RESULTS: Resorcinolnaphthalein caused 
      significant activation of ACE2 in both normal and diseased rats in 7 days after 
      treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 
      days after monocrotaline injection, and the rats developed severe PAH in 21 days 
      with high PAP, right ventricular hypertrophy and neointimal formation. Treatment 
      with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused 
      an improved endothelia-dependent vasorelaxation and decrease in proinflammatory 
      cytokines (tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 
      (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in 
      the early stage of the pathogenesis. CONCLUSIONS: These results demonstrated that 
      activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the 
      development of PAH through improving early endothelial dysfunction and mediating 
      the level of proinflammatory and anti-inflammatory cytokines.
FAU - Li, Gang
AU  - Li G
AD  - Pediatric Center of Cardiac Surgery, Cardiovascular Institute and Fuwai Hospital, 
      Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 
      100037, China.
FAU - Xu, Yu-lin
AU  - Xu YL
FAU - Ling, Feng
AU  - Ling F
FAU - Liu, Ai-jun
AU  - Liu AJ
FAU - Wang, Dong
AU  - Wang D
FAU - Wang, Qiang
AU  - Wang Q
FAU - Liu, Ying-long
AU  - Liu YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Cytokines)
RN  - 0 (Resorcinols)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.17.23 (Ace2 protein, rat)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2
MH  - Animals
MH  - Cytokines/*biosynthesis
MH  - Endothelium, Vascular/*physiology
MH  - Enzyme Activation/drug effects
MH  - Familial Primary Pulmonary Hypertension
MH  - Hypertension, Pulmonary/enzymology/*prevention & control
MH  - Inflammation/prevention & control
MH  - Male
MH  - Peptidyl-Dipeptidase A/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Resorcinols/pharmacology
EDAT- 2012/05/23 06:00
MHDA- 2012/09/19 06:00
CRDT- 2012/05/23 06:00
PHST- 2012/05/23 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2012 Apr;125(8):1381-8.