Kirsty M M Vincent,Terence Garner,Adam Stevens,Elizabeth C Cottrell,Jenny E Myers,Lucy E Higgins
{"title":"低PlGF百分数妊娠中胎盘功能障碍亚型的评估。","authors":"Kirsty M M Vincent,Terence Garner,Adam Stevens,Elizabeth C Cottrell,Jenny E Myers,Lucy E Higgins","doi":"10.1161/hypertensionaha.124.24440","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nA low circulating placental growth factor (PlGF) concentration is considered a marker of placental dysfunction, the predominant cause of preeclampsia and fetal growth restriction. Besides iatrogenic delivery, there are no effective treatments, potentially due to its heterogeneity. We hypothesize that >1 subtype of placental dysfunction exists in pregnancies with a low circulating PlGF.\r\n\r\nMETHODS\r\nMatched placental villous and maternal plasma samples (low PlGF <5th, n=19; normal PlGF ≥5th centile, n=20) were collected from uncomplicated pregnancies and those complicated by 1 or a combination of preeclampsia, fetal growth restriction, or chronic hypertension. Transcriptomic and metabolomic data sets were obtained from villous samples and used to perform cluster-of-cluster analysis. Clinical outcomes were compared between clusters, as well as subsequent pathway analysis.\r\n\r\nRESULTS\r\nMultiomic cluster-of-cluster analysis resulted in 3 molecular clusters. Cluster 1 predominantly consisted of those with a low PlGF (9/10); PlGF results in cluster 2 varied (low, n=8/20; normal, n=12/20), while cluster 3 mainly comprised of those with a normal PlGF result (n=7/9). Birthweight was significantly lower in cluster 1, as well as an increased incidence of early-onset preeclampsia. However, pathways commonly associated with placental dysfunction were only identified in cluster 2.\r\n\r\nCONCLUSIONS\r\nMultiomic analysis revealed 2 potential subtypes of placental dysfunction associated with a low circulating PlGF. These results support previous studies suggesting the existence of preeclampsia subtypes. Clinical outcome comparisons indicate cluster 1 as the severe subtype; however, pathway analysis contradicted this. Improved understanding of subtype etiology could enable a more personalized therapeutic approach for pregnancies complicated by placental dysfunction.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"18 1","pages":""},"PeriodicalIF":6.9000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessing Placental Dysfunction Subtypes in Pregnancies With a Low PlGF Centile.\",\"authors\":\"Kirsty M M Vincent,Terence Garner,Adam Stevens,Elizabeth C Cottrell,Jenny E Myers,Lucy E Higgins\",\"doi\":\"10.1161/hypertensionaha.124.24440\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\r\\nA low circulating placental growth factor (PlGF) concentration is considered a marker of placental dysfunction, the predominant cause of preeclampsia and fetal growth restriction. Besides iatrogenic delivery, there are no effective treatments, potentially due to its heterogeneity. We hypothesize that >1 subtype of placental dysfunction exists in pregnancies with a low circulating PlGF.\\r\\n\\r\\nMETHODS\\r\\nMatched placental villous and maternal plasma samples (low PlGF <5th, n=19; normal PlGF ≥5th centile, n=20) were collected from uncomplicated pregnancies and those complicated by 1 or a combination of preeclampsia, fetal growth restriction, or chronic hypertension. Transcriptomic and metabolomic data sets were obtained from villous samples and used to perform cluster-of-cluster analysis. Clinical outcomes were compared between clusters, as well as subsequent pathway analysis.\\r\\n\\r\\nRESULTS\\r\\nMultiomic cluster-of-cluster analysis resulted in 3 molecular clusters. Cluster 1 predominantly consisted of those with a low PlGF (9/10); PlGF results in cluster 2 varied (low, n=8/20; normal, n=12/20), while cluster 3 mainly comprised of those with a normal PlGF result (n=7/9). Birthweight was significantly lower in cluster 1, as well as an increased incidence of early-onset preeclampsia. However, pathways commonly associated with placental dysfunction were only identified in cluster 2.\\r\\n\\r\\nCONCLUSIONS\\r\\nMultiomic analysis revealed 2 potential subtypes of placental dysfunction associated with a low circulating PlGF. These results support previous studies suggesting the existence of preeclampsia subtypes. Clinical outcome comparisons indicate cluster 1 as the severe subtype; however, pathway analysis contradicted this. Improved understanding of subtype etiology could enable a more personalized therapeutic approach for pregnancies complicated by placental dysfunction.\",\"PeriodicalId\":13042,\"journal\":{\"name\":\"Hypertension\",\"volume\":\"18 1\",\"pages\":\"\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-05-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hypertension\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/hypertensionaha.124.24440\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hypertension","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/hypertensionaha.124.24440","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Assessing Placental Dysfunction Subtypes in Pregnancies With a Low PlGF Centile.
BACKGROUND
A low circulating placental growth factor (PlGF) concentration is considered a marker of placental dysfunction, the predominant cause of preeclampsia and fetal growth restriction. Besides iatrogenic delivery, there are no effective treatments, potentially due to its heterogeneity. We hypothesize that >1 subtype of placental dysfunction exists in pregnancies with a low circulating PlGF.
METHODS
Matched placental villous and maternal plasma samples (low PlGF <5th, n=19; normal PlGF ≥5th centile, n=20) were collected from uncomplicated pregnancies and those complicated by 1 or a combination of preeclampsia, fetal growth restriction, or chronic hypertension. Transcriptomic and metabolomic data sets were obtained from villous samples and used to perform cluster-of-cluster analysis. Clinical outcomes were compared between clusters, as well as subsequent pathway analysis.
RESULTS
Multiomic cluster-of-cluster analysis resulted in 3 molecular clusters. Cluster 1 predominantly consisted of those with a low PlGF (9/10); PlGF results in cluster 2 varied (low, n=8/20; normal, n=12/20), while cluster 3 mainly comprised of those with a normal PlGF result (n=7/9). Birthweight was significantly lower in cluster 1, as well as an increased incidence of early-onset preeclampsia. However, pathways commonly associated with placental dysfunction were only identified in cluster 2.
CONCLUSIONS
Multiomic analysis revealed 2 potential subtypes of placental dysfunction associated with a low circulating PlGF. These results support previous studies suggesting the existence of preeclampsia subtypes. Clinical outcome comparisons indicate cluster 1 as the severe subtype; however, pathway analysis contradicted this. Improved understanding of subtype etiology could enable a more personalized therapeutic approach for pregnancies complicated by placental dysfunction.
期刊介绍:
Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.