Minimally modified low-density lipoprotein upregulates mouse mesenteric arterial 5-HT 1B receptor in vivo via activation of the JAK2/STAT3 pathway

To explore whether minimally modified low-density lipoprotein (mmLDL) upregulates mesenteric arterial 5-hydroxytryptamine 1B (5-HT ) receptor expression by activating the JAK2/STAT3 signaling pathway. Mice were randomly divided into the following groups: the normal saline (NS), LDL, mmLDL, mmLDL+gal...

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Veröffentlicht in:Microvascular research 2022-01, Vol.139, p.104260
Hauptverfasser: Tang, Hong-Xia, Lin, Jie, Xu, Cang-Bao, Chen, Gen, Liao, Ya-Jie, Lei, Ning-Ren, Li, Jie
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container_start_page 104260
container_title Microvascular research
container_volume 139
creator Tang, Hong-Xia
Lin, Jie
Xu, Cang-Bao
Chen, Gen
Liao, Ya-Jie
Lei, Ning-Ren
Li, Jie
description To explore whether minimally modified low-density lipoprotein (mmLDL) upregulates mesenteric arterial 5-hydroxytryptamine 1B (5-HT ) receptor expression by activating the JAK2/STAT3 signaling pathway. Mice were randomly divided into the following groups: the normal saline (NS), LDL, mmLDL, mmLDL+galiellactone (GL, a JAK2/STAT3 pathway inhibitor), and mmLDL+DMSO groups. The dose-response curve of mesenteric arterial ring constriction after administration of 5-carboxamidotryptamine (5-CT), an agonist of 5-HT , was recorded with a microvascular tensiometer. JAK2, p-JAK2, STAT3, p-STAT3, and 5-HT receptor protein expression levels were determined by Western blotting. 5-HT receptor mRNA levels were measured by RT-PCR. 5-HT receptor protein expression was determined by immunofluorescence. Injection of mmLDL into the tail vein significantly increased the contractile dose-response curve after 5-CT stimulation, as the E was 82.15 ± 6.15% in the NS group and 171.88 ± 5.78% in the mmLDL group (P 
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Mice were randomly divided into the following groups: the normal saline (NS), LDL, mmLDL, mmLDL+galiellactone (GL, a JAK2/STAT3 pathway inhibitor), and mmLDL+DMSO groups. The dose-response curve of mesenteric arterial ring constriction after administration of 5-carboxamidotryptamine (5-CT), an agonist of 5-HT , was recorded with a microvascular tensiometer. JAK2, p-JAK2, STAT3, p-STAT3, and 5-HT receptor protein expression levels were determined by Western blotting. 5-HT receptor mRNA levels were measured by RT-PCR. 5-HT receptor protein expression was determined by immunofluorescence. Injection of mmLDL into the tail vein significantly increased the contractile dose-response curve after 5-CT stimulation, as the E was 82.15 ± 6.15% in the NS group and 171.88 ± 5.78% in the mmLDL group (P &lt; 0.01); significantly elevated 5-HT receptor mRNA and protein expression levels; and significantly increased p-JAK2 and p-STAT3 protein expression levels. After intraperitoneal injection of GL, the vasoconstrictive response was significantly reduced compared with that in the mmLDL group, as the E was decreased to 97.14 ± 1.20% (P &lt; 0.01); 5-HT receptor mRNA and protein expression levels were significantly reduced; STAT3 phosphorylation and p-JAK2 and p-STAT3 protein expression were not significantly changed; and 5-HT receptor expression was altered via inhibition of p-STAT3 binding to DNA, which suppressed transcription. mmLDL can upregulate 5-HT receptor expression in mouse mesenteric arteries by activating the JAK2/STAT3 signaling pathway.</description><identifier>EISSN: 1095-9319</identifier><identifier>PMID: 34624308</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Enzyme Activation ; Female ; Janus Kinase 2 - metabolism ; Lipoproteins, LDL - pharmacology ; Male ; Mesenteric Arteries - drug effects ; Mesenteric Arteries - enzymology ; Mice ; Phosphorylation ; Receptor, Serotonin, 5-HT1B - genetics ; Receptor, Serotonin, 5-HT1B - metabolism ; Signal Transduction ; STAT3 Transcription Factor - metabolism ; Up-Regulation ; Vasoconstriction - drug effects</subject><ispartof>Microvascular research, 2022-01, Vol.139, p.104260</ispartof><rights>Copyright © 2021. 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Mice were randomly divided into the following groups: the normal saline (NS), LDL, mmLDL, mmLDL+galiellactone (GL, a JAK2/STAT3 pathway inhibitor), and mmLDL+DMSO groups. The dose-response curve of mesenteric arterial ring constriction after administration of 5-carboxamidotryptamine (5-CT), an agonist of 5-HT , was recorded with a microvascular tensiometer. JAK2, p-JAK2, STAT3, p-STAT3, and 5-HT receptor protein expression levels were determined by Western blotting. 5-HT receptor mRNA levels were measured by RT-PCR. 5-HT receptor protein expression was determined by immunofluorescence. Injection of mmLDL into the tail vein significantly increased the contractile dose-response curve after 5-CT stimulation, as the E was 82.15 ± 6.15% in the NS group and 171.88 ± 5.78% in the mmLDL group (P &lt; 0.01); significantly elevated 5-HT receptor mRNA and protein expression levels; and significantly increased p-JAK2 and p-STAT3 protein expression levels. After intraperitoneal injection of GL, the vasoconstrictive response was significantly reduced compared with that in the mmLDL group, as the E was decreased to 97.14 ± 1.20% (P &lt; 0.01); 5-HT receptor mRNA and protein expression levels were significantly reduced; STAT3 phosphorylation and p-JAK2 and p-STAT3 protein expression were not significantly changed; and 5-HT receptor expression was altered via inhibition of p-STAT3 binding to DNA, which suppressed transcription. mmLDL can upregulate 5-HT receptor expression in mouse mesenteric arteries by activating the JAK2/STAT3 signaling pathway.</description><subject>Animals</subject><subject>Enzyme Activation</subject><subject>Female</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Male</subject><subject>Mesenteric Arteries - drug effects</subject><subject>Mesenteric Arteries - enzymology</subject><subject>Mice</subject><subject>Phosphorylation</subject><subject>Receptor, Serotonin, 5-HT1B - genetics</subject><subject>Receptor, Serotonin, 5-HT1B - metabolism</subject><subject>Signal Transduction</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Up-Regulation</subject><subject>Vasoconstriction - drug effects</subject><issn>1095-9319</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFj8FKw0AURQdBbK3-grwfCGYyjZhlFaVUXJl9eU1e7JPJzDDzkpLf8ItNQddu7tmcC_deqKXOqzKrjK4W6jqlrzzXuqyKK7Uw64dibfLHpfp-Z8c9WjtB71vumFqw_pS15BLLBJaDD9ELsYMhRPocLAqlWR4SQU-JnFDkBjCeiRbKbFuDfoJIDQXxEebmyKOfAwEb4RGFvQPfgRwJdpu34v6j3tQGAsrxhNONuuzQJrr95Urdvb7Uz9ssDIee2n2I8-A47f9OmH-FH1ehVB0</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Tang, Hong-Xia</creator><creator>Lin, Jie</creator><creator>Xu, Cang-Bao</creator><creator>Chen, Gen</creator><creator>Liao, Ya-Jie</creator><creator>Lei, Ning-Ren</creator><creator>Li, Jie</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>202201</creationdate><title>Minimally modified low-density lipoprotein upregulates mouse mesenteric arterial 5-HT 1B receptor in vivo via activation of the JAK2/STAT3 pathway</title><author>Tang, Hong-Xia ; Lin, Jie ; Xu, Cang-Bao ; Chen, Gen ; Liao, Ya-Jie ; Lei, Ning-Ren ; Li, Jie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_346243083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Enzyme Activation</topic><topic>Female</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Male</topic><topic>Mesenteric Arteries - drug effects</topic><topic>Mesenteric Arteries - enzymology</topic><topic>Mice</topic><topic>Phosphorylation</topic><topic>Receptor, Serotonin, 5-HT1B - genetics</topic><topic>Receptor, Serotonin, 5-HT1B - metabolism</topic><topic>Signal Transduction</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Up-Regulation</topic><topic>Vasoconstriction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Hong-Xia</creatorcontrib><creatorcontrib>Lin, Jie</creatorcontrib><creatorcontrib>Xu, Cang-Bao</creatorcontrib><creatorcontrib>Chen, Gen</creatorcontrib><creatorcontrib>Liao, Ya-Jie</creatorcontrib><creatorcontrib>Lei, Ning-Ren</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Microvascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Hong-Xia</au><au>Lin, Jie</au><au>Xu, Cang-Bao</au><au>Chen, Gen</au><au>Liao, Ya-Jie</au><au>Lei, Ning-Ren</au><au>Li, Jie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minimally modified low-density lipoprotein upregulates mouse mesenteric arterial 5-HT 1B receptor in vivo via activation of the JAK2/STAT3 pathway</atitle><jtitle>Microvascular research</jtitle><addtitle>Microvasc Res</addtitle><date>2022-01</date><risdate>2022</risdate><volume>139</volume><spage>104260</spage><pages>104260-</pages><eissn>1095-9319</eissn><abstract>To explore whether minimally modified low-density lipoprotein (mmLDL) upregulates mesenteric arterial 5-hydroxytryptamine 1B (5-HT ) receptor expression by activating the JAK2/STAT3 signaling pathway. Mice were randomly divided into the following groups: the normal saline (NS), LDL, mmLDL, mmLDL+galiellactone (GL, a JAK2/STAT3 pathway inhibitor), and mmLDL+DMSO groups. The dose-response curve of mesenteric arterial ring constriction after administration of 5-carboxamidotryptamine (5-CT), an agonist of 5-HT , was recorded with a microvascular tensiometer. JAK2, p-JAK2, STAT3, p-STAT3, and 5-HT receptor protein expression levels were determined by Western blotting. 5-HT receptor mRNA levels were measured by RT-PCR. 5-HT receptor protein expression was determined by immunofluorescence. Injection of mmLDL into the tail vein significantly increased the contractile dose-response curve after 5-CT stimulation, as the E was 82.15 ± 6.15% in the NS group and 171.88 ± 5.78% in the mmLDL group (P &lt; 0.01); significantly elevated 5-HT receptor mRNA and protein expression levels; and significantly increased p-JAK2 and p-STAT3 protein expression levels. After intraperitoneal injection of GL, the vasoconstrictive response was significantly reduced compared with that in the mmLDL group, as the E was decreased to 97.14 ± 1.20% (P &lt; 0.01); 5-HT receptor mRNA and protein expression levels were significantly reduced; STAT3 phosphorylation and p-JAK2 and p-STAT3 protein expression were not significantly changed; and 5-HT receptor expression was altered via inhibition of p-STAT3 binding to DNA, which suppressed transcription. mmLDL can upregulate 5-HT receptor expression in mouse mesenteric arteries by activating the JAK2/STAT3 signaling pathway.</abstract><cop>United States</cop><pmid>34624308</pmid></addata></record>
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subjects Animals
Enzyme Activation
Female
Janus Kinase 2 - metabolism
Lipoproteins, LDL - pharmacology
Male
Mesenteric Arteries - drug effects
Mesenteric Arteries - enzymology
Mice
Phosphorylation
Receptor, Serotonin, 5-HT1B - genetics
Receptor, Serotonin, 5-HT1B - metabolism
Signal Transduction
STAT3 Transcription Factor - metabolism
Up-Regulation
Vasoconstriction - drug effects
title Minimally modified low-density lipoprotein upregulates mouse mesenteric arterial 5-HT 1B receptor in vivo via activation of the JAK2/STAT3 pathway
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