Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI
    • الموضوع:
      Mice, Inbred C57BL* ; Endothelial Cells*/metabolism ; Endothelial Cells*/drug effects ; Alcohol Drinking*/adverse effects ; Ethanol*/pharmacology ; Intramolecular Oxidoreductases*/metabolism; Animals ; Male ; Mice ; Lipocalins/metabolism ; Lipocalins/genetics ; Anti-Inflammatory Agents/pharmacology ; Inflammation/pathology ; Cell Proliferation/drug effects ; Neovascularization, Physiologic/drug effects ; Brain/pathology ; Brain/drug effects ; Brain/metabolism ; Brain/blood supply
    • نبذة مختصرة :
      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.
    • Grant Information:
      2R01AA023610-07A1 United States NH NIH HHS
    • Contributed Indexing:
      Keywords: L-PGDS; alcohol; angiogenesis; inflammation; ischemic stroke
    • الرقم المعرف:
      EC 5.3.99.2 (prostaglandin R2 D-isomerase)
      3K9958V90M (Ethanol)
      EC 5.3.- (Intramolecular Oxidoreductases)
      0 (Lipocalins)
      0 (Anti-Inflammatory Agents)
    • الموضوع:
      Date Created: 20241217 Date Completed: 20241217 Latest Revision: 20241217
    • الموضوع:
      20241217
    • الرقم المعرف:
      10.3390/cells13232007
    • الرقم المعرف:
      39682755