The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption
Light alcohol consumption (LAC) may reduce the incidence and improve the prognosis of ischemic stroke. Recently, we found that LAC promotes cerebral angiogenesis and inhibits early inflammation following ischemic stroke. In addition, LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS)...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/23/2007 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850106598574260224 |
|---|---|
| author | Jiyu Li Chun Li Utsab Subedi Pushpa Subedi Manikandan Panchatcharam Hong Sun |
| author_facet | Jiyu Li Chun Li Utsab Subedi Pushpa Subedi Manikandan Panchatcharam Hong Sun |
| author_sort | Jiyu Li |
| collection | DOAJ |
| description | Light alcohol consumption (LAC) may reduce the incidence and improve the prognosis of ischemic stroke. Recently, we found that LAC promotes cerebral angiogenesis and inhibits early inflammation following ischemic stroke. In addition, LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS) in the brain. Thus, we determined the role of endothelial L-PGDS in the protective effect of LAC. In in vitro studies, chronic exposure to low-concentration ethanol upregulated L-PGDS and significantly increased the proliferation in cultured C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). AT-56, a selective L-PGDS inhibitor, abolished low-concentration ethanol exposure-induced proliferation. In in vivo studies, 8-week gavage feeding with 0.7 g/kg/day ethanol, defined as LAC, promoted cerebral angiogenesis under physiological conditions and following ischemic stroke in male C57BL/6J mice. In addition, LAC inhibited the post-ischemic expression of adhesion molecules, neutrophil infiltration, and microglial activation. AT-56 and endothelial cell (EC)-specific L-PGDS conditional knockout did not significantly alter cerebral angiogenesis and post-ischemic inflammation in the control mice but eliminated the pro-angiogenic and anti-inflammatory effects of LAC. Furthermore, EC-specific L-PGDS conditional knockout alleviated the neuroprotective effect of LAC against cerebral ischemia/reperfusion injury. These findings suggest that endothelial L-PGDS may be crucial in the pro-angiogenic and anti-inflammatory effects of LAC against ischemic stroke. |
| format | Article |
| id | doaj-art-b0caca7d011e422eb79da3b42e4d4bc3 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-b0caca7d011e422eb79da3b42e4d4bc32025-08-20T02:38:47ZengMDPI AGCells2073-44092024-12-011323200710.3390/cells13232007The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol ConsumptionJiyu Li0Chun Li1Utsab Subedi2Pushpa Subedi3Manikandan Panchatcharam4Hong Sun5Department of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USALight alcohol consumption (LAC) may reduce the incidence and improve the prognosis of ischemic stroke. Recently, we found that LAC promotes cerebral angiogenesis and inhibits early inflammation following ischemic stroke. In addition, LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS) in the brain. Thus, we determined the role of endothelial L-PGDS in the protective effect of LAC. In in vitro studies, chronic exposure to low-concentration ethanol upregulated L-PGDS and significantly increased the proliferation in cultured C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). AT-56, a selective L-PGDS inhibitor, abolished low-concentration ethanol exposure-induced proliferation. In in vivo studies, 8-week gavage feeding with 0.7 g/kg/day ethanol, defined as LAC, promoted cerebral angiogenesis under physiological conditions and following ischemic stroke in male C57BL/6J mice. In addition, LAC inhibited the post-ischemic expression of adhesion molecules, neutrophil infiltration, and microglial activation. AT-56 and endothelial cell (EC)-specific L-PGDS conditional knockout did not significantly alter cerebral angiogenesis and post-ischemic inflammation in the control mice but eliminated the pro-angiogenic and anti-inflammatory effects of LAC. Furthermore, EC-specific L-PGDS conditional knockout alleviated the neuroprotective effect of LAC against cerebral ischemia/reperfusion injury. These findings suggest that endothelial L-PGDS may be crucial in the pro-angiogenic and anti-inflammatory effects of LAC against ischemic stroke.https://www.mdpi.com/2073-4409/13/23/2007alcoholL-PGDSangiogenesisinflammationischemic stroke |
| spellingShingle | Jiyu Li Chun Li Utsab Subedi Pushpa Subedi Manikandan Panchatcharam Hong Sun The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption Cells alcohol L-PGDS angiogenesis inflammation ischemic stroke |
| title | The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption |
| title_full | The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption |
| title_fullStr | The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption |
| title_full_unstemmed | The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption |
| title_short | The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption |
| title_sort | role of endothelial l pgds in the pro angiogenic and anti inflammatory effects of low dose alcohol consumption |
| topic | alcohol L-PGDS angiogenesis inflammation ischemic stroke |
| url | https://www.mdpi.com/2073-4409/13/23/2007 |
| work_keys_str_mv | AT jiyuli theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT chunli theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT utsabsubedi theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT pushpasubedi theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT manikandanpanchatcharam theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT hongsun theroleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT jiyuli roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT chunli roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT utsabsubedi roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT pushpasubedi roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT manikandanpanchatcharam roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption AT hongsun roleofendotheliallpgdsintheproangiogenicandantiinflammatoryeffectsoflowdosealcoholconsumption |