Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells
Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating mono...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/7039854 |
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| author | Yunfei Chai Runying Yu Yong Liu Sheng Wang Dongdong Yuan Jimei Chen |
| author_facet | Yunfei Chai Runying Yu Yong Liu Sheng Wang Dongdong Yuan Jimei Chen |
| author_sort | Yunfei Chai |
| collection | DOAJ |
| description | Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways. |
| format | Article |
| id | doaj-art-58ca151009204dfbb3f4542f446381ef |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-58ca151009204dfbb3f4542f446381ef2025-02-03T01:05:23ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/70398547039854Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial CellsYunfei Chai0Runying Yu1Yong Liu2Sheng Wang3Dongdong Yuan4Jimei Chen5Anesthesiology Department of Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, ChinaOperating Centre of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, ChinaDepartment of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Peoples Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, ChinaDepartment of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, ChinaDepartment of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, ChinaCurrent studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways.http://dx.doi.org/10.1155/2020/7039854 |
| spellingShingle | Yunfei Chai Runying Yu Yong Liu Sheng Wang Dongdong Yuan Jimei Chen Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells Mediators of Inflammation |
| title | Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells |
| title_full | Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells |
| title_fullStr | Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells |
| title_full_unstemmed | Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells |
| title_short | Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells |
| title_sort | dexmedetomidine attenuates monocyte endothelial adherence via inhibiting connexin43 on vascular endothelial cells |
| url | http://dx.doi.org/10.1155/2020/7039854 |
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