دورية أكاديمية
Metabolic signatures of pregnancy-induced cardiac growth.
| العنوان: | Metabolic signatures of pregnancy-induced cardiac growth. |
|---|---|
| المؤلفون: | Fulghum KL; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Smith JB; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Chariker J; Kentucky INBRE Genomics Core, University of Louisville, Louisville, Kentucky., Garrett LF; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Brittian KR; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Lorkiewicz PK; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., McNally LA; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Uchida S; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark., Jones SP; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Hill BG; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky., Collins HE; Diabetes and Obesity Center, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky. |
| المصدر: | American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2022 Jul 01; Vol. 323 (1), pp. H146-H164. Date of Electronic Publication: 2022 May 27. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Heart* , Proteomics*, Animals ; Cardiomegaly/metabolism ; Female ; Mice ; Mitochondria, Heart/metabolism ; Myocardium/metabolism ; Oxidation-Reduction ; Pregnancy |
| مستخلص: | The goal of this study was to develop an atlas of the metabolic, transcriptional, and proteomic changes that occur with pregnancy in the maternal heart. Timed pregnancy studies in FVB/NJ mice revealed a significant increase in heart size by day 8 of pregnancy (midpregnancy; MP), which was sustained throughout the rest of the term compared with nonpregnant control mice. Cardiac hypertrophy and myocyte cross-sectional area were highest 7 days after birth (postbirth; PB) and were associated with significant increases in end-diastolic and end-systolic left ventricular volumes and higher cardiac output. Metabolomics analyses revealed that by day 16 of pregnancy (late pregnancy; LP) metabolites associated with nitric oxide production as well as acylcholines, sphingomyelins, and fatty acid species were elevated, which coincided with a lower activation state of phosphofructokinase and higher levels of pyruvate dehydrogenase kinase 4 (Pdk4) and β-hydroxybutyrate dehydrogenase 1 (Bdh1). In the postpartum period, urea cycle metabolites, polyamines, and phospholipid levels were markedly elevated in the maternal heart. Cardiac transcriptomics in LP revealed significant increases in not only Pdk4 and Bdh1 but also genes that regulate glutamate and ketone body oxidation, which were preceded in MP by higher expression of transcripts controlling cell proliferation and angiogenesis. Proteomics analysis of the maternal heart in LP and PB revealed significant reductions in several contractile filament and mitochondrial subunit complex proteins. Collectively, these findings describe the coordinated molecular changes that occur in the maternal heart during and after pregnancy. NEW & NOTEWORTHY Little is known of the underlying molecular and cellular mechanisms that contribute to pregnancy-induced cardiac growth. Several lines of evidence suggest that changes in cardiac metabolism may contribute. Here, we provide a comprehensive metabolic atlas of the metabolomic, proteomic, and transcriptomic changes occurring in the maternal heart. We show that pregnancy-induced cardiac growth is associated with changes in glycerophospholipid, nucleotide, and amino acid metabolism, with reductions in cardiac glucose catabolism. Collectively, these results suggest that substantial metabolic changes occur in the maternal heart during and after pregnancy. |
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| معلومات مُعتمدة: | HL154663 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); GM103436 HHS | NIH | National Institute of General Medical Sciences (NIGMS); GM127607 HHS | NIH | National Institute of General Medical Sciences (NIGMS); P30 GM127607 United States GM NIGMS NIH HHS; R24 GM137786 United States GM NIGMS NIH HHS; R01 HL147844 United States HL NHLBI NIH HHS; P20 GM103436 United States GM NIGMS NIH HHS; HL147844 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); F31 HL154663 United States HL NHLBI NIH HHS; S10 OD025178 United States OD NIH HHS; S10OD025178 HHS | National Institutes of Health (NIH) |
| فهرسة مساهمة: | Keywords: hypertrophy; metabolomics; pregnancy; proteomics; transcriptomics |
| سلسلة جزيئية: | figshare 10.6084/m9.figshare.19651137 |
| تواريخ الأحداث: | Date Created: 20220527 Date Completed: 20220629 Latest Revision: 20230703 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9236881 |
| DOI: | 10.1152/ajpheart.00105.2022 |
| PMID: | 35622533 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1539 |
|---|---|
| DOI: | 10.1152/ajpheart.00105.2022 |