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Disruption of the Apelin-APJ System Worsens Hypoxia-Induced Pulmonary Hypertension
| Content Provider | Scilit |
|---|---|
| Author | Chandra, Suparna M. Razavi, Hedi Kim, Jongmin Agrawal, Rani Kundu, Ramendra K. Perez, Vinicio De Jesus Zamanian, Roham T. Quertermous, Thomas Chun, Hyung J. |
| Copyright Year | 2011 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective—: The G-protein–coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH). Methods and Results—: We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Micro-computed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2 (KLF2), a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and KLF2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls. Conclusion—: These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease. |
| Related Links | http://atvb.ahajournals.org/content/31/4/814.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113525/pdf https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.110.219980 |
| Ending Page | 820 |
| Page Count | 7 |
| Starting Page | 814 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.110.219980 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 4 |
| Volume Number | 31 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2011-04-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Peripheral Vascular Disease Pulmonary Hypertension Amp-activated Kinase Endothelial Function Nitric Oxide Synthase |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
