Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype
Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated b...
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| Veröffentlicht in: | Placenta (Eastbourne) 2022-03, Vol.119, p.52-62 |
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| creator | Briffa, J.F. Bevens, W. Gravina, S. Said, J.M. Wlodek, M.E. |
| description | Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated by fetal growth restriction and pre-eclampsia. Importantly, biglycan stimulates angiogenesis in numerous tissues. Therefore, this study investigated whether biglycan knockdown in mice results in a pre-eclamptic phenotype.
Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent post-mortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected.
Bgn-/- dams had increased heart rate (+9%, p |
| doi_str_mv | 10.1016/j.placenta.2022.02.002 |
| format | Article |
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Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent post-mortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected.
Bgn-/- dams had increased heart rate (+9%, p < 0.037) and reduced systolic (−11%, p < 0.001), diastolic (−15%, p < 0.001), and mean arterial (−12%, p < 0.001) pressures at all ages investigated compared to WT. Additionally, Bgn-/- dams had reduced urine flow rate (−64%, p < 0.001) as well as reduced urinary excretions (−49%, p < 0.004) during late gestation compared to WT. Bgn-/- pups had higher body weight (+8%, p = 0.004; E18 only) and a higher liver-to-brain weight ratio (+43%, p < 0.001). Placental weight was unaltered with only minor changes in vasculogenic and angiogenic gene abundances detected, which did not correlate to changes in protein expression.
This study demonstrated that total knockdown of biglycan is not associated with features of pre-eclampsia.
•Biglycan is reduced in pre-eclampsia and silencing biglycan impairs angiogenesis.•Biglycan knockdown (Bgn−/−) alters maternal cardiorenal adaptations to pregnancy.•Biglycan deficiency has a protective effect against fetal growth restriction.•Minimal changes were observed in markers of placental vasculogenic/angiogenic.•Total knockdown of biglycan does not result in a pre-eclamptic phenotype.]]></description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2022.02.002</identifier><identifier>PMID: 35150975</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adaptation, Physiological ; Angiogenesis ; Animals ; Biglycan ; Biglycan - physiology ; Female ; Male ; Maternal cardiorenal health ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neovascularization, Physiologic ; Placenta ; Pre-Eclampsia - etiology ; Pregnancy ; Vascularization</subject><ispartof>Placenta (Eastbourne), 2022-03, Vol.119, p.52-62</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c315t-cbd12ce37fd8ae8934c43a0b7d163e6ba7d962585efabc1880c3432b8ee0e1873</cites><orcidid>0000-0001-5173-4790 ; 0000-0002-8490-9099 ; 0000-0001-6944-6500</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0143400422000376$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35150975$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Briffa, J.F.</creatorcontrib><creatorcontrib>Bevens, W.</creatorcontrib><creatorcontrib>Gravina, S.</creatorcontrib><creatorcontrib>Said, J.M.</creatorcontrib><creatorcontrib>Wlodek, M.E.</creatorcontrib><title>Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><description><![CDATA[Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated by fetal growth restriction and pre-eclampsia. Importantly, biglycan stimulates angiogenesis in numerous tissues. Therefore, this study investigated whether biglycan knockdown in mice results in a pre-eclamptic phenotype.
Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent post-mortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected.
Bgn-/- dams had increased heart rate (+9%, p < 0.037) and reduced systolic (−11%, p < 0.001), diastolic (−15%, p < 0.001), and mean arterial (−12%, p < 0.001) pressures at all ages investigated compared to WT. Additionally, Bgn-/- dams had reduced urine flow rate (−64%, p < 0.001) as well as reduced urinary excretions (−49%, p < 0.004) during late gestation compared to WT. Bgn-/- pups had higher body weight (+8%, p = 0.004; E18 only) and a higher liver-to-brain weight ratio (+43%, p < 0.001). Placental weight was unaltered with only minor changes in vasculogenic and angiogenic gene abundances detected, which did not correlate to changes in protein expression.
This study demonstrated that total knockdown of biglycan is not associated with features of pre-eclampsia.
•Biglycan is reduced in pre-eclampsia and silencing biglycan impairs angiogenesis.•Biglycan knockdown (Bgn−/−) alters maternal cardiorenal adaptations to pregnancy.•Biglycan deficiency has a protective effect against fetal growth restriction.•Minimal changes were observed in markers of placental vasculogenic/angiogenic.•Total knockdown of biglycan does not result in a pre-eclamptic phenotype.]]></description><subject>Adaptation, Physiological</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biglycan</subject><subject>Biglycan - physiology</subject><subject>Female</subject><subject>Male</subject><subject>Maternal cardiorenal health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neovascularization, Physiologic</subject><subject>Placenta</subject><subject>Pre-Eclampsia - etiology</subject><subject>Pregnancy</subject><subject>Vascularization</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYsLAL4y8ZEGHst2v7EAjXtJIsIC1VW1XEmfcdmM7kfId_DAeZYYtUkl3UefWQ5exGwFrAaJ_f1gvHg2FgmsJUq6hFshnbCU6JRslQD5nKxCtalqA9oq9yvkAAJtWyJfsSnWig83QrdifH4l2AUPhk9v5s8HA70M09_FY-OwM8T2eiKMvlMhyg8m6mCig52hxKVhcDJljsBx53sdUOb6jfGlUylPYlf07PtV5NvIQq9CJfFyqYUnUkPE4L8UZvuypts8LvWYvtugzvXnUa_br86eft1-bu-9fvt1-vGuMEl1pzGSFNKSGrR2Rxo1qTasQpsGKXlE_4WA3vezGjrY4GTGOYFSr5DQSAYlxUNfs7WXukuLvYz1azy4b8h4DxWPWspejAlDtpqL9BTUp5pxoq5fkZkxnLUA_BKIP-ikQ_RCIhlogq_Hmccdxmsn-sz0lUIEPF4DqpydHSWfjKBiyLpEp2kb3vx1_ARapo2Q</recordid><startdate>20220304</startdate><enddate>20220304</enddate><creator>Briffa, J.F.</creator><creator>Bevens, W.</creator><creator>Gravina, S.</creator><creator>Said, J.M.</creator><creator>Wlodek, M.E.</creator><general>Elsevier Ltd</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><orcidid>https://orcid.org/0000-0001-5173-4790</orcidid><orcidid>https://orcid.org/0000-0002-8490-9099</orcidid><orcidid>https://orcid.org/0000-0001-6944-6500</orcidid></search><sort><creationdate>20220304</creationdate><title>Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype</title><author>Briffa, J.F. ; Bevens, W. ; Gravina, S. ; Said, J.M. ; Wlodek, M.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-cbd12ce37fd8ae8934c43a0b7d163e6ba7d962585efabc1880c3432b8ee0e1873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adaptation, Physiological</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biglycan</topic><topic>Biglycan - physiology</topic><topic>Female</topic><topic>Male</topic><topic>Maternal cardiorenal health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neovascularization, Physiologic</topic><topic>Placenta</topic><topic>Pre-Eclampsia - etiology</topic><topic>Pregnancy</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Briffa, J.F.</creatorcontrib><creatorcontrib>Bevens, W.</creatorcontrib><creatorcontrib>Gravina, S.</creatorcontrib><creatorcontrib>Said, J.M.</creatorcontrib><creatorcontrib>Wlodek, M.E.</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>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Briffa, J.F.</au><au>Bevens, W.</au><au>Gravina, S.</au><au>Said, J.M.</au><au>Wlodek, M.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2022-03-04</date><risdate>2022</risdate><volume>119</volume><spage>52</spage><epage>62</epage><pages>52-62</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><abstract><![CDATA[Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated by fetal growth restriction and pre-eclampsia. Importantly, biglycan stimulates angiogenesis in numerous tissues. Therefore, this study investigated whether biglycan knockdown in mice results in a pre-eclamptic phenotype.
Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent post-mortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected.
Bgn-/- dams had increased heart rate (+9%, p < 0.037) and reduced systolic (−11%, p < 0.001), diastolic (−15%, p < 0.001), and mean arterial (−12%, p < 0.001) pressures at all ages investigated compared to WT. Additionally, Bgn-/- dams had reduced urine flow rate (−64%, p < 0.001) as well as reduced urinary excretions (−49%, p < 0.004) during late gestation compared to WT. Bgn-/- pups had higher body weight (+8%, p = 0.004; E18 only) and a higher liver-to-brain weight ratio (+43%, p < 0.001). Placental weight was unaltered with only minor changes in vasculogenic and angiogenic gene abundances detected, which did not correlate to changes in protein expression.
This study demonstrated that total knockdown of biglycan is not associated with features of pre-eclampsia.
•Biglycan is reduced in pre-eclampsia and silencing biglycan impairs angiogenesis.•Biglycan knockdown (Bgn−/−) alters maternal cardiorenal adaptations to pregnancy.•Biglycan deficiency has a protective effect against fetal growth restriction.•Minimal changes were observed in markers of placental vasculogenic/angiogenic.•Total knockdown of biglycan does not result in a pre-eclamptic phenotype.]]></abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>35150975</pmid><doi>10.1016/j.placenta.2022.02.002</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5173-4790</orcidid><orcidid>https://orcid.org/0000-0002-8490-9099</orcidid><orcidid>https://orcid.org/0000-0001-6944-6500</orcidid></addata></record> |
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| subjects | Adaptation, Physiological Angiogenesis Animals Biglycan Biglycan - physiology Female Male Maternal cardiorenal health Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Physiologic Placenta Pre-Eclampsia - etiology Pregnancy Vascularization |
| title | Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype |
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