# Preserved Function of Endothelial Colony-Forming Cells in Female Rats with Intrauterine Growth Restriction: Protection Against Arterial Hypertension and Arterial Stiffness?

## TL;DR

Female rats with intrauterine growth restriction show preserved endothelial cell function, which may protect them from vascular issues like high blood pressure.

## Contribution

The study reveals sexual dimorphism in vascular outcomes of IUGR rats, with preserved ECFC function in females offering protection against hypertension and arterial stiffness.

## Key findings

- IUGR female rats show preserved ECFC function and no significant vascular dysfunction at 6 months.
- ECFCs from IUGR females have minor changes in proliferation but maintain capillary-like structure formation.
- IUGR females have decreased aortic collagen and increased elastin, suggesting structural vascular protection.

## Abstract

What are the main findings?
Intrauterine growth restriction (IUGR) is a risk factor for long-term vascular outcomes.A sexual dimorphism has been identified: compared to control, only IUGR male rats displayed vascular dysfunctions at 6 months of age.

Intrauterine growth restriction (IUGR) is a risk factor for long-term vascular outcomes.

A sexual dimorphism has been identified: compared to control, only IUGR male rats displayed vascular dysfunctions at 6 months of age.

What are the implications of the main findings?
IUGR female rats show only minor changes in endothelial colony forming cells (ECFCs) functions.The absence of ECFC alterations could protect IUGR females against vascular dysfunctions.

IUGR female rats show only minor changes in endothelial colony forming cells (ECFCs) functions.

The absence of ECFC alterations could protect IUGR females against vascular dysfunctions.

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31+/CD146+ ratio among viable CD45− cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness.