Gojnić-Dugalić, Miroslava

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

Abstract Context Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. Objective To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. Design and Intervention FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling. Settings and Participants Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. Main Outcome Measures Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed. Results The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis. Conclusions The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.