Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy
Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompan...
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creator | Tocantins, Carolina Martins, João D. Rodrigues, Óscar M. Grilo, Luís F. Diniz, Mariana S. Stevanovic-Silva, Jelena Beleza, Jorge Coxito, Pedro Rizo-Roca, David Santos-Alves, Estela Moreno, António J. Ascensão, António Magalhães, José Oliveira, Paulo J. Pereira, Susana P. |
description | Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.
[Display omitted]
•Pregnancy-associated heart molecular adaptations remain eight weeks postpartum.•Activated cardiac AMPKα and Hif1α are increased in postpartum hearts.•Increased mitochondrial ATP and NADH were found postpartum in cardiac tissue.•Augmented Nrf2 and GPX4 levels and catalase activity exist in postpartum hearts.•Cardiac redox state is imbalanced at late postpartum (2.6× gestation time). |
doi_str_mv | 10.1016/j.bbadis.2024.167539 |
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[Display omitted]
•Pregnancy-associated heart molecular adaptations remain eight weeks postpartum.•Activated cardiac AMPKα and Hif1α are increased in postpartum hearts.•Increased mitochondrial ATP and NADH were found postpartum in cardiac tissue.•Augmented Nrf2 and GPX4 levels and catalase activity exist in postpartum hearts.•Cardiac redox state is imbalanced at late postpartum (2.6× gestation time).</description><identifier>ISSN: 0925-4439</identifier><identifier>ISSN: 1879-260X</identifier><identifier>EISSN: 1879-260X</identifier><identifier>DOI: 10.1016/j.bbadis.2024.167539</identifier><identifier>PMID: 39378968</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adaptation, Physiological ; AMP-Activated Protein Kinases - metabolism ; Animals ; Cardiac health post-pregnancy ; Cardiac metabolic flexibility ; Cardiac redox balance postpartum ; Female ; Heart ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Lactation - metabolism ; Maternal cardiovascular health ; Myocardium - metabolism ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Oxidation-Reduction ; Postpartum cardiac remodeling ; Postpartum Period - metabolism ; PPAR alpha - genetics ; PPAR alpha - metabolism ; Pregnancy ; Pregnancy-induced heart molecular adaptations ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Biochimica et biophysica acta. Molecular basis of disease, 2025-01, Vol.1871 (1), p.167539, Article 167539</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c241t-388d721233e183c15b6c203e5f1c249f7140a159a411a17f0b8eb4a3eaa671793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbadis.2024.167539$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39378968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tocantins, Carolina</creatorcontrib><creatorcontrib>Martins, João D.</creatorcontrib><creatorcontrib>Rodrigues, Óscar M.</creatorcontrib><creatorcontrib>Grilo, Luís F.</creatorcontrib><creatorcontrib>Diniz, Mariana S.</creatorcontrib><creatorcontrib>Stevanovic-Silva, Jelena</creatorcontrib><creatorcontrib>Beleza, Jorge</creatorcontrib><creatorcontrib>Coxito, Pedro</creatorcontrib><creatorcontrib>Rizo-Roca, David</creatorcontrib><creatorcontrib>Santos-Alves, Estela</creatorcontrib><creatorcontrib>Moreno, António J.</creatorcontrib><creatorcontrib>Ascensão, António</creatorcontrib><creatorcontrib>Magalhães, José</creatorcontrib><creatorcontrib>Oliveira, Paulo J.</creatorcontrib><creatorcontrib>Pereira, Susana P.</creatorcontrib><title>Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy</title><title>Biochimica et biophysica acta. Molecular basis of disease</title><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><description>Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.
[Display omitted]
•Pregnancy-associated heart molecular adaptations remain eight weeks postpartum.•Activated cardiac AMPKα and Hif1α are increased in postpartum hearts.•Increased mitochondrial ATP and NADH were found postpartum in cardiac tissue.•Augmented Nrf2 and GPX4 levels and catalase activity exist in postpartum hearts.•Cardiac redox state is imbalanced at late postpartum (2.6× gestation time).</description><subject>Adaptation, Physiological</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Cardiac health post-pregnancy</subject><subject>Cardiac metabolic flexibility</subject><subject>Cardiac redox balance postpartum</subject><subject>Female</subject><subject>Heart</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Lactation - metabolism</subject><subject>Maternal cardiovascular health</subject><subject>Myocardium - metabolism</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Postpartum cardiac remodeling</subject><subject>Postpartum Period - metabolism</subject><subject>PPAR alpha - genetics</subject><subject>PPAR alpha - metabolism</subject><subject>Pregnancy</subject><subject>Pregnancy-induced heart molecular adaptations</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0925-4439</issn><issn>1879-260X</issn><issn>1879-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EotvCGyCUI5csHtuJ4wtSVRWoVMSlSNysiTOhXiVxsL2ofXtcZemRuczl-__RfIy9A74HDu3Hw77vcfBpL7hQe2h1I80LtoNOm1q0_OdLtuNGNLVS0pyx85QOvEyr-Wt2Jo3UnWm7Hbv7hpniglN1TxhzRQ_3vvc5VTNl7MPkXYXLUEUawkOFA64Zsw9LqtaQcn1cXJjXApWSoVoj_VpwcY9v2KsRp0RvT_uC_fh8fXf1tb79_uXm6vK2dkJBrmXXDVqAkJKgkw6avnWCS2pGKIAZNSiO0BhUAAh65H1HvUJJiK0GbeQF-7D1rjH8PlLKdvbJ0TThQuGYrARQyhRQFFRtqIshpUijXaOfMT5a4PbJpz3Yzad98mk3nyX2_nTh2M80PIf-CSzApw2g8ucfT9Em52lxNPhILtsh-P9f-AtUwYil</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Tocantins, Carolina</creator><creator>Martins, João D.</creator><creator>Rodrigues, Óscar M.</creator><creator>Grilo, Luís F.</creator><creator>Diniz, Mariana S.</creator><creator>Stevanovic-Silva, Jelena</creator><creator>Beleza, Jorge</creator><creator>Coxito, Pedro</creator><creator>Rizo-Roca, David</creator><creator>Santos-Alves, Estela</creator><creator>Moreno, António J.</creator><creator>Ascensão, António</creator><creator>Magalhães, José</creator><creator>Oliveira, Paulo J.</creator><creator>Pereira, Susana P.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202501</creationdate><title>Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy</title><author>Tocantins, Carolina ; Martins, João D. ; Rodrigues, Óscar M. ; Grilo, Luís F. ; Diniz, Mariana S. ; Stevanovic-Silva, Jelena ; Beleza, Jorge ; Coxito, Pedro ; Rizo-Roca, David ; Santos-Alves, Estela ; Moreno, António J. ; Ascensão, António ; Magalhães, José ; Oliveira, Paulo J. ; Pereira, Susana P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-388d721233e183c15b6c203e5f1c249f7140a159a411a17f0b8eb4a3eaa671793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Adaptation, Physiological</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Cardiac health post-pregnancy</topic><topic>Cardiac metabolic flexibility</topic><topic>Cardiac redox balance postpartum</topic><topic>Female</topic><topic>Heart</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Lactation - metabolism</topic><topic>Maternal cardiovascular health</topic><topic>Myocardium - metabolism</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Postpartum cardiac remodeling</topic><topic>Postpartum Period - metabolism</topic><topic>PPAR alpha - genetics</topic><topic>PPAR alpha - metabolism</topic><topic>Pregnancy</topic><topic>Pregnancy-induced heart molecular adaptations</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tocantins, Carolina</creatorcontrib><creatorcontrib>Martins, João D.</creatorcontrib><creatorcontrib>Rodrigues, Óscar M.</creatorcontrib><creatorcontrib>Grilo, Luís F.</creatorcontrib><creatorcontrib>Diniz, Mariana S.</creatorcontrib><creatorcontrib>Stevanovic-Silva, Jelena</creatorcontrib><creatorcontrib>Beleza, Jorge</creatorcontrib><creatorcontrib>Coxito, Pedro</creatorcontrib><creatorcontrib>Rizo-Roca, David</creatorcontrib><creatorcontrib>Santos-Alves, Estela</creatorcontrib><creatorcontrib>Moreno, António J.</creatorcontrib><creatorcontrib>Ascensão, António</creatorcontrib><creatorcontrib>Magalhães, José</creatorcontrib><creatorcontrib>Oliveira, Paulo J.</creatorcontrib><creatorcontrib>Pereira, Susana P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tocantins, Carolina</au><au>Martins, João D.</au><au>Rodrigues, Óscar M.</au><au>Grilo, Luís F.</au><au>Diniz, Mariana S.</au><au>Stevanovic-Silva, Jelena</au><au>Beleza, Jorge</au><au>Coxito, Pedro</au><au>Rizo-Roca, David</au><au>Santos-Alves, Estela</au><au>Moreno, António J.</au><au>Ascensão, António</au><au>Magalhães, José</au><au>Oliveira, Paulo J.</au><au>Pereira, Susana P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy</atitle><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><date>2025-01</date><risdate>2025</risdate><volume>1871</volume><issue>1</issue><spage>167539</spage><pages>167539-</pages><artnum>167539</artnum><issn>0925-4439</issn><issn>1879-260X</issn><eissn>1879-260X</eissn><abstract>Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.
[Display omitted]
•Pregnancy-associated heart molecular adaptations remain eight weeks postpartum.•Activated cardiac AMPKα and Hif1α are increased in postpartum hearts.•Increased mitochondrial ATP and NADH were found postpartum in cardiac tissue.•Augmented Nrf2 and GPX4 levels and catalase activity exist in postpartum hearts.•Cardiac redox state is imbalanced at late postpartum (2.6× gestation time).</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39378968</pmid><doi>10.1016/j.bbadis.2024.167539</doi></addata></record> |
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subjects | Adaptation, Physiological AMP-Activated Protein Kinases - metabolism Animals Cardiac health post-pregnancy Cardiac metabolic flexibility Cardiac redox balance postpartum Female Heart Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Lactation - metabolism Maternal cardiovascular health Myocardium - metabolism NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Oxidation-Reduction Postpartum cardiac remodeling Postpartum Period - metabolism PPAR alpha - genetics PPAR alpha - metabolism Pregnancy Pregnancy-induced heart molecular adaptations Rats Rats, Sprague-Dawley |
title | Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy |
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