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

• Published in: International journal of molecular sciences 2021-09, Vol.22 (18), p.10159
• Main Authors: Simoncini, Stephanie, Coppola, Hanna, Rocca, Angela, Bachmann, Isaline, Guillot, Estelle, Zippo, Leila, Dignat-George, Françoise, Sabatier, Florence, Bedel, Romain, Wilson, Anne, Rosenblatt-Velin, Nathalie, Armengaud, Jean-Baptiste, Menétrey, Steeve, Peyter, Anne-Christine, Simeoni, Umberto, Yzydorczyk, Catherine
• Format: Article
• Language: English
• Subjects: Adults; Angiogenesis; Animals; arterial hypertension; Birth weight; Blood pressure; Blood Pressure - physiology; Bone marrow; Cardiovascular disease; CD34 antigen; CD45 antigen; Cell proliferation; Cell Proliferation - physiology; Cellular Senescence - physiology; Colonies; Colony-forming cells; Cord blood; developmental programming; DNA damage; endothelial colony-forming cells; Endothelium; Female; Fetal Growth Retardation - physiopathology; Flow cytometry; Fluorescent dyes; Fluorescent indicators; Galactosidase; Gene expression; Gestation; Hypertension; Immunofluorescence; INK4a protein; intrauterine growth restriction; Life Sciences; Low birth weight; Low protein diet; Male; Males; Microvasculature; Neonates; Neovascularization, Pathologic - physiopathology; Newborn babies; Nutrient deficiency; Oxidative stress; Oxidative Stress - physiology; Plethysmography; Protein expression; Proteins; Rarefaction; Rats; Senescence; stress-induced premature senescence; Superoxide dismutase; Vascular endothelial growth factor; β-Galactosidase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms221810159

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 , 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.