Clara Liu Chung Ming, Dillan Pienaar, Sahar Ghorbanpour, Hao Chen, Lynne Margaret Roberts, Louise Cole, Kristine C McGrath, Matthew P Padula, Amanda Henry, Carmine Gentile, Lana McClements
{"title":"产后心血管健康的三维体外建模揭示了妊娠期高血压疾病的独特特征和特征。","authors":"Clara Liu Chung Ming, Dillan Pienaar, Sahar Ghorbanpour, Hao Chen, Lynne Margaret Roberts, Louise Cole, Kristine C McGrath, Matthew P Padula, Amanda Henry, Carmine Gentile, Lana McClements","doi":"10.1186/s13293-024-00672-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.</p><p><strong>Methods: </strong>Human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).</p><p><strong>Results: </strong>Contraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).</p><p><strong>Conclusions: </strong>The innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"94"},"PeriodicalIF":4.9000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587612/pdf/","citationCount":"0","resultStr":"{\"title\":\"3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.\",\"authors\":\"Clara Liu Chung Ming, Dillan Pienaar, Sahar Ghorbanpour, Hao Chen, Lynne Margaret Roberts, Louise Cole, Kristine C McGrath, Matthew P Padula, Amanda Henry, Carmine Gentile, Lana McClements\",\"doi\":\"10.1186/s13293-024-00672-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.</p><p><strong>Methods: </strong>Human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).</p><p><strong>Results: </strong>Contraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).</p><p><strong>Conclusions: </strong>The innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.</p>\",\"PeriodicalId\":8890,\"journal\":{\"name\":\"Biology of Sex Differences\",\"volume\":\"15 1\",\"pages\":\"94\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-11-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587612/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biology of Sex Differences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13293-024-00672-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Sex Differences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13293-024-00672-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
背景:妊娠期高血压疾病(HDP)影响2-8%的妊娠,并与产后心血管疾病(CVD)风险增加有关,但其机制尚不清楚。方法:将诱导多能干细胞(iPSC)衍生的心肌细胞、心脏成纤维细胞和冠状动脉内皮细胞进行共培养,在含有产后五年收集的10%患者血浆的1型胶原水凝胶中形成心脏球体(CSs)[每组5个:正常血压对照组、妊娠高血压组(GH)和子痫前期组(PE)]。对血浆处理过的CS进行细胞活力和收缩功能评估,并进行免疫荧光染色和成像。对血浆样本进行了定量蛋白质组分析(对照组 n = 21;GH n = 5;PE n = 12):结果:经 PE 处理的 CS 收缩频率(CF)增加(CF:45.5 ± 3.4 次收缩/分钟,p 结论:经 PE 处理的 CS 收缩频率(CF)增加(CF:45.5 ± 3.4 次收缩/分钟,p):创新的患者相关 CS 平台发现了与 GH 诱导的心血管疾病中的细胞死亡信号转导和心脏重塑以及 PE 诱导的心血管疾病中的血管/内皮细胞功能障碍相关的生物标记物/靶标。
3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.
Background: Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.
Methods: Human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).
Results: Contraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).
Conclusions: The innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.
期刊介绍:
Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research.
Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.