Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM
Gestational diabetes mellitus (GDM) increases risk of adverse pregnancy outcomes and maternal cardiovascular complications. It is widely believed that maternal endothelial dysfunction is a critical determinant of these risks, however, connections to maternal cardiac dysfunction and mechanisms of pat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4970 |
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| author | Stephanie M. Kereliuk Fengxia Xiao Dylan Burger Vernon W. Dolinsky |
| author_facet | Stephanie M. Kereliuk Fengxia Xiao Dylan Burger Vernon W. Dolinsky |
| author_sort | Stephanie M. Kereliuk |
| collection | DOAJ |
| description | Gestational diabetes mellitus (GDM) increases risk of adverse pregnancy outcomes and maternal cardiovascular complications. It is widely believed that maternal endothelial dysfunction is a critical determinant of these risks, however, connections to maternal cardiac dysfunction and mechanisms of pathogenesis are unclear. Circulating extracellular vesicles (EVs) are emerging biomarkers that may provide insights into the pathogenesis of GDM. We examined the impact of GDM on maternal cardiac and vascular health in a rat model of diet-induced obesity-associated GDM. We observed a >3-fold increase in circulating levels of endothelial EVs (<i>p</i> < 0.01) and von Willebrand factor (<i>p</i> < 0.001) in GDM rats. A significant increase in mitochondrial DNA (mtDNA) within circulating extracellular vesicles was also observed suggesting possible mitochondrial dysfunction in the vasculature. This was supported by nicotinamide adenine dinucleotide deficiency in aortas of GDM mice. GDM was also associated with cardiac remodeling (increased LV mass) and a marked impairment in maternal diastolic function (increased isovolumetric relaxation time [IVRT], <i>p</i> < 0.01). Finally, we observed a strong positive correlation between endothelial EV levels and IVRT (r = 0.57, <i>p</i> < 0.05). In summary, we observed maternal vascular and cardiac dysfunction in rodent GDM accompanied by increased circulating endothelial EVs and EV-associated mitochondrial DNA. Our study highlights a novel method for assessment of vascular injury in GDM and highlights vascular mitochondrial injury as a possible therapeutic target. |
| first_indexed | 2024-03-10T04:05:34Z |
| format | Article |
| id | doaj.art-9d0a950f36b74156ba1efcc515cd4d92 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:34Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d0a950f36b74156ba1efcc515cd4d922023-11-23T08:25:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239497010.3390/ijms23094970Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDMStephanie M. Kereliuk0Fengxia Xiao1Dylan Burger2Vernon W. Dolinsky3Diabetes Research Envisioned and Accomplished in Manitoba (DREAM), Research Theme of the Children’s Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, CanadaKidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 7N9, CanadaKidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 7N9, CanadaDiabetes Research Envisioned and Accomplished in Manitoba (DREAM), Research Theme of the Children’s Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, CanadaGestational diabetes mellitus (GDM) increases risk of adverse pregnancy outcomes and maternal cardiovascular complications. It is widely believed that maternal endothelial dysfunction is a critical determinant of these risks, however, connections to maternal cardiac dysfunction and mechanisms of pathogenesis are unclear. Circulating extracellular vesicles (EVs) are emerging biomarkers that may provide insights into the pathogenesis of GDM. We examined the impact of GDM on maternal cardiac and vascular health in a rat model of diet-induced obesity-associated GDM. We observed a >3-fold increase in circulating levels of endothelial EVs (<i>p</i> < 0.01) and von Willebrand factor (<i>p</i> < 0.001) in GDM rats. A significant increase in mitochondrial DNA (mtDNA) within circulating extracellular vesicles was also observed suggesting possible mitochondrial dysfunction in the vasculature. This was supported by nicotinamide adenine dinucleotide deficiency in aortas of GDM mice. GDM was also associated with cardiac remodeling (increased LV mass) and a marked impairment in maternal diastolic function (increased isovolumetric relaxation time [IVRT], <i>p</i> < 0.01). Finally, we observed a strong positive correlation between endothelial EV levels and IVRT (r = 0.57, <i>p</i> < 0.05). In summary, we observed maternal vascular and cardiac dysfunction in rodent GDM accompanied by increased circulating endothelial EVs and EV-associated mitochondrial DNA. Our study highlights a novel method for assessment of vascular injury in GDM and highlights vascular mitochondrial injury as a possible therapeutic target.https://www.mdpi.com/1422-0067/23/9/4970extracellular vesiclespregnancydiabetesgestational diabetesmitochondria |
| spellingShingle | Stephanie M. Kereliuk Fengxia Xiao Dylan Burger Vernon W. Dolinsky Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM International Journal of Molecular Sciences extracellular vesicles pregnancy diabetes gestational diabetes mitochondria |
| title | Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM |
| title_full | Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM |
| title_fullStr | Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM |
| title_full_unstemmed | Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM |
| title_short | Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM |
| title_sort | extracellular vesicles as an index for endothelial injury and cardiac dysfunction in a rodent model of gdm |
| topic | extracellular vesicles pregnancy diabetes gestational diabetes mitochondria |
| url | https://www.mdpi.com/1422-0067/23/9/4970 |
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