Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

Aim Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidativ...

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Veröffentlicht in:Acta Physiologica 2019-11, Vol.227 (3), p.e13328-n/a
Hauptverfasser: Krause, Bernardo J., Peñaloza, Estefanía, Candia, Alejandro, Cañas, Daniel, Hernández, Cherie, Arenas, German A., Peralta‐Scholz, María José, Valenzuela, Rodrigo, García‐Herrera, Claudio, Herrera, Emilio A.
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container_issue 3
container_start_page e13328
container_title Acta Physiologica
container_volume 227
creator Krause, Bernardo J.
Peñaloza, Estefanía
Candia, Alejandro
Cañas, Daniel
Hernández, Cherie
Arenas, German A.
Peralta‐Scholz, María José
Valenzuela, Rodrigo
García‐Herrera, Claudio
Herrera, Emilio A.
description Aim Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P 
doi_str_mv 10.1111/apha.13328
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Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05). Conclusion Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.]]></description><identifier>ISSN: 1748-1708</identifier><identifier>EISSN: 1748-1716</identifier><identifier>DOI: 10.1111/apha.13328</identifier><identifier>PMID: 31177629</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Aorta ; Cardiovascular diseases ; Carotid artery ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Endothelial cells ; endothelial function ; Epigenetics ; Femur ; foetal growth restriction ; Mechanical properties ; mRNA ; NOS3 ; Oxidative stress</subject><ispartof>Acta Physiologica, 2019-11, Vol.227 (3), p.e13328-n/a</ispartof><rights>2019 Scandinavian Physiological Society. Published by John Wiley &amp; Sons Ltd</rights><rights>2019 Scandinavian Physiological Society. 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Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05). Conclusion Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.]]></description><subject>Aorta</subject><subject>Cardiovascular diseases</subject><subject>Carotid artery</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Endothelial cells</subject><subject>endothelial function</subject><subject>Epigenetics</subject><subject>Femur</subject><subject>foetal growth restriction</subject><subject>Mechanical properties</subject><subject>mRNA</subject><subject>NOS3</subject><subject>Oxidative stress</subject><issn>1748-1708</issn><issn>1748-1716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc9O3DAQh62qCBDshQeoLHFBSEv9J4nNMaJQKqGFQ3u2JhNnY5SNFzvpam99gUo8Y5-kDks5cKgvtsefvhnrR8gJZxc8rc-wbuGCSyn0B3LIVabnXPHi49uZ6QMyi_GRMcYFl5kQ--RAcq5UIS4Pye-yHruB_oSIYweB1tvYjD0OzvfU9bTxdoCOLoPfDO2fX8_BxiE4HGxNl6PrLaTa2i0jdZFCjB4dTG8bN7QUaG99n-6JgZcuMdWxdf1yUi98lPTLoqQrO7TbDqaWx2SvgS7a2et-RH7cXH-_up3f3X_9dlXezVHmSs8zYQsNtVXIsKoqsKiw0lhXucosZlrlddboAnMGTINGkFkOWGhdo7INr-QROdt518E_jelPZuUi2q6DNPIYjRB5wZnUOkvo6Tv00Y-hT9MZIRlX8lKIIlHnOwqDjzHYxqyDW0HYGs7MlJOZcjIvOSX406tyrFa2fkP_pZIAvgM2rrPb_6hM-XBb7qR_AfXso0Y</recordid><startdate>201911</startdate><enddate>201911</enddate><creator>Krause, Bernardo J.</creator><creator>Peñaloza, Estefanía</creator><creator>Candia, Alejandro</creator><creator>Cañas, Daniel</creator><creator>Hernández, Cherie</creator><creator>Arenas, German A.</creator><creator>Peralta‐Scholz, María José</creator><creator>Valenzuela, Rodrigo</creator><creator>García‐Herrera, Claudio</creator><creator>Herrera, Emilio A.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3563-6143</orcidid></search><sort><creationdate>201911</creationdate><title>Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation</title><author>Krause, Bernardo J. ; Peñaloza, Estefanía ; Candia, Alejandro ; Cañas, Daniel ; Hernández, Cherie ; Arenas, German A. ; Peralta‐Scholz, María José ; Valenzuela, Rodrigo ; García‐Herrera, Claudio ; Herrera, Emilio A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3578-42e68ade7c0cbbbaec7cb8cdb574ec4875d4f86c50a08a8ca345ac688dc7ef1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aorta</topic><topic>Cardiovascular diseases</topic><topic>Carotid artery</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Endothelial cells</topic><topic>endothelial function</topic><topic>Epigenetics</topic><topic>Femur</topic><topic>foetal growth restriction</topic><topic>Mechanical properties</topic><topic>mRNA</topic><topic>NOS3</topic><topic>Oxidative stress</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krause, Bernardo J.</creatorcontrib><creatorcontrib>Peñaloza, Estefanía</creatorcontrib><creatorcontrib>Candia, Alejandro</creatorcontrib><creatorcontrib>Cañas, Daniel</creatorcontrib><creatorcontrib>Hernández, Cherie</creatorcontrib><creatorcontrib>Arenas, German A.</creatorcontrib><creatorcontrib>Peralta‐Scholz, María José</creatorcontrib><creatorcontrib>Valenzuela, Rodrigo</creatorcontrib><creatorcontrib>García‐Herrera, Claudio</creatorcontrib><creatorcontrib>Herrera, Emilio A.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>MEDLINE - Academic</collection><jtitle>Acta Physiologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krause, Bernardo J.</au><au>Peñaloza, Estefanía</au><au>Candia, Alejandro</au><au>Cañas, Daniel</au><au>Hernández, Cherie</au><au>Arenas, German A.</au><au>Peralta‐Scholz, María José</au><au>Valenzuela, Rodrigo</au><au>García‐Herrera, Claudio</au><au>Herrera, Emilio A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation</atitle><jtitle>Acta Physiologica</jtitle><addtitle>Acta Physiol (Oxf)</addtitle><date>2019-11</date><risdate>2019</risdate><volume>227</volume><issue>3</issue><spage>e13328</spage><epage>n/a</epage><pages>e13328-n/a</pages><issn>1748-1708</issn><eissn>1748-1716</eissn><abstract><![CDATA[Aim Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05). Conclusion Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.]]></abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31177629</pmid><doi>10.1111/apha.13328</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-3563-6143</orcidid></addata></record>
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source Wiley Online Library Journals Frontfile Complete
subjects Aorta
Cardiovascular diseases
Carotid artery
Deoxyribonucleic acid
DNA
DNA methylation
Endothelial cells
endothelial function
Epigenetics
Femur
foetal growth restriction
Mechanical properties
mRNA
NOS3
Oxidative stress
title Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation
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