Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice

Chronic alcohol consumption dose-dependently affects the incidence and prognosis of ischemic stroke. We determined the influence of chronic alcohol consumption on cerebral angiogenesis under physiological conditions and following ischemic stroke. In in vitro studies, acute exposure to low-concentrat...

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Autores principales: Jiyu Li, Chun Li, Ethyn G. Loreno, Sumitra Miriyala, Manikandan Panchatcharam, Xiaohong Lu, Hong Sun
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/4803d1a38d35445cbe4207d8eaccc77e
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spelling oai:doaj.org-article:4803d1a38d35445cbe4207d8eaccc77e2021-11-17T05:03:54ZChronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice2297-055X10.3389/fcvm.2021.681627https://doaj.org/article/4803d1a38d35445cbe4207d8eaccc77e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.681627/fullhttps://doaj.org/toc/2297-055XChronic alcohol consumption dose-dependently affects the incidence and prognosis of ischemic stroke. We determined the influence of chronic alcohol consumption on cerebral angiogenesis under physiological conditions and following ischemic stroke. In in vitro studies, acute exposure to low-concentration ethanol significantly increased angiogenic capability and upregulated vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). The increased angiogenic capability was abolished in the presence of a VEGFR2 inhibitor. In addition, the increased angiogenic capability and upregulated VEGF-A and VEGFR2 remained in chronically low-concentration ethanol-exposed MBMVECs. In in vivo studies, 8-week gavage feeding with low-dose ethanol significantly increased vessel density and vessel branches and upregulated VEGF-A and VEGFR2 in the cerebral cortex under physiological conditions. Furthermore, vessel density, vessel branches, and expression of VEGF-A and VEGFR2 in the peri-infarct cortex were significantly greater in low-dose ethanol-fed mice at 72 h of reperfusion. Although low-dose ethanol did not alter cerebral vasoreactivity and regional cerebral blood flow (rCBF) either before or during ischemia, it significantly augmented post-ischemic hyperemia during reperfusion. In contrast, exposure to high-concentration ethanol and 8-week gavage feeding with high-dose ethanol only had a mild inhibitory effect on angiogenic capability and cerebral angiogenesis, respectively. We conclude that heavy alcohol consumption may not dramatically alter cerebral angiogenesis, whereas light alcohol consumption significantly promotes cerebral angiogenesis.Jiyu LiChun LiEthyn G. LorenoSumitra MiriyalaManikandan PanchatcharamXiaohong LuHong SunFrontiers Media S.A.articlealcoholangiogenesisischemic strokeVEGF-AVEGFR2brainDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic alcohol
angiogenesis
ischemic stroke
VEGF-A
VEGFR2
brain
Diseases of the circulatory (Cardiovascular) system
RC666-701
spellingShingle alcohol
angiogenesis
ischemic stroke
VEGF-A
VEGFR2
brain
Diseases of the circulatory (Cardiovascular) system
RC666-701
Jiyu Li
Chun Li
Ethyn G. Loreno
Sumitra Miriyala
Manikandan Panchatcharam
Xiaohong Lu
Hong Sun
Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
description Chronic alcohol consumption dose-dependently affects the incidence and prognosis of ischemic stroke. We determined the influence of chronic alcohol consumption on cerebral angiogenesis under physiological conditions and following ischemic stroke. In in vitro studies, acute exposure to low-concentration ethanol significantly increased angiogenic capability and upregulated vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). The increased angiogenic capability was abolished in the presence of a VEGFR2 inhibitor. In addition, the increased angiogenic capability and upregulated VEGF-A and VEGFR2 remained in chronically low-concentration ethanol-exposed MBMVECs. In in vivo studies, 8-week gavage feeding with low-dose ethanol significantly increased vessel density and vessel branches and upregulated VEGF-A and VEGFR2 in the cerebral cortex under physiological conditions. Furthermore, vessel density, vessel branches, and expression of VEGF-A and VEGFR2 in the peri-infarct cortex were significantly greater in low-dose ethanol-fed mice at 72 h of reperfusion. Although low-dose ethanol did not alter cerebral vasoreactivity and regional cerebral blood flow (rCBF) either before or during ischemia, it significantly augmented post-ischemic hyperemia during reperfusion. In contrast, exposure to high-concentration ethanol and 8-week gavage feeding with high-dose ethanol only had a mild inhibitory effect on angiogenic capability and cerebral angiogenesis, respectively. We conclude that heavy alcohol consumption may not dramatically alter cerebral angiogenesis, whereas light alcohol consumption significantly promotes cerebral angiogenesis.
format article
author Jiyu Li
Chun Li
Ethyn G. Loreno
Sumitra Miriyala
Manikandan Panchatcharam
Xiaohong Lu
Hong Sun
author_facet Jiyu Li
Chun Li
Ethyn G. Loreno
Sumitra Miriyala
Manikandan Panchatcharam
Xiaohong Lu
Hong Sun
author_sort Jiyu Li
title Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
title_short Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
title_full Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
title_fullStr Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
title_full_unstemmed Chronic Low-Dose Alcohol Consumption Promotes Cerebral Angiogenesis in Mice
title_sort chronic low-dose alcohol consumption promotes cerebral angiogenesis in mice
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/4803d1a38d35445cbe4207d8eaccc77e
work_keys_str_mv AT jiyuli chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT chunli chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT ethyngloreno chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT sumitramiriyala chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT manikandanpanchatcharam chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT xiaohonglu chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
AT hongsun chroniclowdosealcoholconsumptionpromotescerebralangiogenesisinmice
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