Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction

International Journal of Molecular Sciences

卷:22

Françoise Dignat-George¹  Florence Sabatier¹  Stephanie Simoncini¹  Nathalie Rosenblatt-Velin²  Isaline Bachmann³  Hanna Coppola³  Leila Zippo³  Catherine Yzydorczyk³  Jean-Baptiste Armengaud³  Estelle Guillot³  Umberto Simeoni³  Angela Rocca³  Anne-Christine Peyter⁴  Steeve Menétrey⁴  Romain Bedel⁵  Anne Wilson⁵ 

[1] Aix Marseille Univ, Institut National de la Santé Et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAe), Center from Cardiovascular and Nutrition research (C2VN), UMR-S 1263, UFR de Pharmacie, Campus Santé, 13385 Marseille, France;

[2] Department Heart-Vessels, Division of Angiology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;

[3] Department Woman-Mother-Child, Division of pediatrics, DOHaD Laboratory, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;

[4] Department Woman-Mother-Child, Neonatal Research Laboratory, Clinic of Neonatology, Lausanne University Hospital and University of Lausanne, University of Lausanne, 1011 Lausanne, Switzerland;

[5] Flow Cytometry Facility, Department of Formation and Research, University of Lausanne, 1011 Lausanne, Switzerland;

关键词: intrauterine growth restriction;    developmental programming;    arterial hypertension;    endothelial colony-forming cells;    oxidative stress;    stress-induced premature senescence;   

DOI  :  10.3390/ijms221810159

来源: DOAJ

【 摘 要 】

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 p16^INK4a, 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.

【 授权许可】

Unknown