title: Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis prevents lipopolysaccharide-induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF-κB pathways.
abstract: ACE2 and Ang-(1-7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang-(1-7)/Mas axis prevents LPS-induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF-κB pathways. Primary cultured rat PMVECs were transduced with lentiviral-borne Ace2 or shRNA-Ace2, and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang-(1-7), cytokine secretion, and apoptosis rates, and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang-(1-7) levels, thus reducing LPS-induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK, and NF-κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2-induced blockade of p38, JNK, and NF-κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang-(1-7)/Mas axis has a crucial role in preventing LPS-induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF-κB pathways.
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Yingchuan
authors: Y
authors: Li
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Yongmei
authors: Y
authors: Cao
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Zhen
authors: Z
authors: Zeng
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Mengfan
authors: M
authors: Liang
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Ying
authors: Y
authors: Xue
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Caihua
authors: C
authors: Xi
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Ming
authors: M
authors: Zhou
authors: Department of Anesthesiology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Wei
authors: W
authors: Jiang
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D055806:Microvessels / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
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