Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries

Increases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branc...

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Main Authors: Zoltan Nemeth, Krisztian Eros, Gyongyi Munkacsy, Akos Koller
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/6/856
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author Zoltan Nemeth
Krisztian Eros
Gyongyi Munkacsy
Akos Koller
author_facet Zoltan Nemeth
Krisztian Eros
Gyongyi Munkacsy
Akos Koller
author_sort Zoltan Nemeth
collection DOAJ
description Increases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branches to reach certain brain areas. In contrast, increases in flow elicit constrictions in the middle cerebral artery (MCA), supplied by the anterior cerebral circulation (ACC) and regulating the blood pressure and flow in distal cerebral circulation. Mediators of flow-dependent responses include arachidonic acid (AA) metabolites and nitric oxide (NO). We hypothesized that mediators of flow-dependent responses are differentially expressed in cerebral arteries of the PCC (CA<sub>PCC</sub>) and ACC (CA<sub>ACC</sub>). The expressions of key enzymes of the AA pathway—cyclooxygenases (COX1/COX2), cytochrome P450 hydroxylases (Cyp450), thromboxane synthase (TXAS), thromboxane A2 (TP) receptor, prostacyclin synthase (PGIS), prostacyclin (IP) receptor (IP); neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS)—in the BA and MCA from rats (n = 20) were determined by western blotting. Transcriptome analysis in CA<sub>PCC</sub> and CA<sub>ACC</sub> from rats (n = 25) was assessed by RNA sequencing. In BA compared to MCA, COX1/2 and Cyp450 protein expressions were lower, PGIS was higher, TXAS and nNOS/eNOS were similar, TP receptors were lower, and IP receptors were higher. Gene expressions of vasodilator canonical pathways were higher in CA<sub>PCC</sub>; vasoconstriction canonical pathways were higher in CA<sub>ACC</sub>. Mediators of flow-dependent vasomotor signaling are differentially expressed in cerebral arteries of the posterior and anterior circulation, corresponding to their vasomotor function.
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spelling doaj-art-c47ba2c22ccf4c8ba969d22bb99cb0092025-08-20T03:16:18ZengMDPI AGLife2075-17292025-05-0115685610.3390/life15060856Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis ArteriesZoltan Nemeth0Krisztian Eros1Gyongyi Munkacsy2Akos Koller3HUN-REN-SE, Cerebrovascular and Neurocognitive Disease Research Group, Institute of Translational Medicine, Semmelweis University, 1085 Budapest, HungaryDepartment of Biochemistry and Medical Chemistry, Medical School, University of Pecs, 7624 Pecs, HungaryDepartment of Bioinformatics, Semmelweis University, 1085 Budapest, HungaryHUN-REN-SE, Cerebrovascular and Neurocognitive Disease Research Group, Institute of Translational Medicine, Semmelweis University, 1085 Budapest, HungaryIncreases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branches to reach certain brain areas. In contrast, increases in flow elicit constrictions in the middle cerebral artery (MCA), supplied by the anterior cerebral circulation (ACC) and regulating the blood pressure and flow in distal cerebral circulation. Mediators of flow-dependent responses include arachidonic acid (AA) metabolites and nitric oxide (NO). We hypothesized that mediators of flow-dependent responses are differentially expressed in cerebral arteries of the PCC (CA<sub>PCC</sub>) and ACC (CA<sub>ACC</sub>). The expressions of key enzymes of the AA pathway—cyclooxygenases (COX1/COX2), cytochrome P450 hydroxylases (Cyp450), thromboxane synthase (TXAS), thromboxane A2 (TP) receptor, prostacyclin synthase (PGIS), prostacyclin (IP) receptor (IP); neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS)—in the BA and MCA from rats (n = 20) were determined by western blotting. Transcriptome analysis in CA<sub>PCC</sub> and CA<sub>ACC</sub> from rats (n = 25) was assessed by RNA sequencing. In BA compared to MCA, COX1/2 and Cyp450 protein expressions were lower, PGIS was higher, TXAS and nNOS/eNOS were similar, TP receptors were lower, and IP receptors were higher. Gene expressions of vasodilator canonical pathways were higher in CA<sub>PCC</sub>; vasoconstriction canonical pathways were higher in CA<sub>ACC</sub>. Mediators of flow-dependent vasomotor signaling are differentially expressed in cerebral arteries of the posterior and anterior circulation, corresponding to their vasomotor function.https://www.mdpi.com/2075-1729/15/6/856cerebral blood flow regulationmechano-transductionsmall cerebral arteriesarachidonic acid metabolismnitric oxide signaling
spellingShingle Zoltan Nemeth
Krisztian Eros
Gyongyi Munkacsy
Akos Koller
Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
Life
cerebral blood flow regulation
mechano-transduction
small cerebral arteries
arachidonic acid metabolism
nitric oxide signaling
title Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
title_full Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
title_fullStr Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
title_full_unstemmed Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
title_short Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries
title_sort differential gene and protein expressions responsible for vasomotor signaling provide mechanistic bases for the opposite flow induced responses of pre and post circle of willis arteries
topic cerebral blood flow regulation
mechano-transduction
small cerebral arteries
arachidonic acid metabolism
nitric oxide signaling
url https://www.mdpi.com/2075-1729/15/6/856
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