Hypoxia-induced downregulation of Sema3a and CXCL12/CXCR4 regulate the formation of the coronary artery stem at the proper site
| Autor: | Tatsuya Kamimura, Mayu Narematsu, Toshiyuki Yamagishi, Yuji Nakajima |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Receptors CXCR4 Down-Regulation In situ hybridization 030204 cardiovascular system & hematology Quail 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine.artery medicine Animals Progenitor cell Hypoxia Molecular Biology Aorta Cells Cultured Chemistry Endothelial Cells Semaphorin-3A Hypoxia (medical) Embryonic stem cell Coronary Vessels Chemokine CXCL12 Cell biology Up-Regulation 030104 developmental biology medicine.anatomical_structure Pulmonary artery medicine.symptom Cardiology and Cardiovascular Medicine Chickens Artery |
| Zdroj: | Journal of molecular and cellular cardiology. 147 |
| ISSN: | 1095-8584 |
| Popis: | Background During the formation of the coronary artery stem, endothelial strands from the endothelial progenitor pool surrounding the conotruncus penetrate into the aortic wall. Vascular endothelial growth factors (VEGFs) as well as CXCL12/CXCR4 signaling are thought to play a role in the formation of the coronary stem. However, the mechanisms regulating how endothelial strands exclusively invade into the aorta remain unknown. Methods and results Immunohistochemistry showed that before the formation of endothelial strands, Sema3a was highly expressed in endothelial progenitors surrounding the great arteries. At the onset of/during invasion of endothelial strands into the aorta, Sema3a was downregulated and CXCR4 was upregulated in the endothelial strands. In situ hybridization showed that Cxcl12 was highly expressed in the aortic wall compared with in the pulmonary artery. Using avian embryonic hearts, we established two types of endothelial penetration assay, in which coronary endothelial strands preferentially invaded into the aorta in culture. Sema3a blocking peptide induced an excess number of endothelial strands penetrating into the pulmonary artery, whereas recombinant Sema3a inhibited the formation of endothelial strands. In cultured coronary endothelial progenitors, recombinant VEGF protein induced CXCR4-positive endothelial strands, which were capable of being attracted by CXCL12-impregnated beads. Monoazo rhodamine detected that hypoxia was predominant in aortic/subaortic region in ovo and hypoxic condition downregulated the expression of Sema3a in culture. Conclusion Results suggested that hypoxia in the aortic region downregulates the expression of Sema3a, thereby enhancing VEGF activity to induce the formation of CXCR4-positive endothelial strands, which are subsequently attracted into the Cxcl12-positive aortic wall to connect the aortic lumen. |
| Databáze: | OpenAIRE |
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