Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction
Creators
- 1. Aix-Marseille University, INSERM, INRA, C2VN, UMR_S 1263, UFR de Pharmacie, Marseille, France
- 2. Department Woman-Mother-Child, Division of pediatrics, DOHaD Laboratory, Lausanne University Hospital & Faculty of Biology and Medicine, University of Lausanne, Switzerland
- 3. Flow Cytometry Facility, Department of Formation and Research, University of Lausanne, Switzerland
- 4. Flow Cytometry Facility, Department of Formation and Research, University of Lausanne, Switzerland; Department of Oncology, University of Lausanne, Switzerland
- 5. Department Heart-Vessels, Division of Angiology, Lausanne University Hospital and Faculty of Biology and Medicine, Lausanne, Switzerland
- 6. Department Woman-Mother-Child, Neonatal Research Laboratory, Clinic of Neonatology, Lausanne University Hospital & Faculty of Biology and Medicine, University of Lausanne, Switzerland
Description
Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.
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