Pericyte Coverage and Microvessel Caliber: Association with Smoking Status and Body‐Mass‐Index in Normal and Pre‐eclamptic Pregnancies

Abstract

Pre‐eclampsia (PE) is a hypertensive disorder of pregnancy that is a major cause of maternal and fetal morbidity and mortality worldwide. Current evidence suggests that PE may result from shallow implantation of the developing fetus into the uterus, leading to abnormal formation of uteroplacental blood vessels. Pericytes play critical roles in neovessel formation and are thought to also have a role in blood flow regulation in microvascular networks. Little is known however about their function in the placenta and how this may be altered in disease. Here, we sought to determine whether differences exist in placental microvessel caliber or pericyte coverage between normal and PE pregnancies. We also examined whether modifiable risk factors might impact the observed phenotypes. Human placental tissue was obtained from normal and PE pregnancies (IRB protocol approved by Carilion Clinic). Tissue sections were antibody labeled, imaged by confocal microscopy, and assessed for vascular‐specific metrics. For comparative analysis, placental tissue from WT mice was sectioned, labeled, and imaged by confocal to optimize protocols and assess for pericyte localization. Measurements were collected using ImageJ/FIJI, and statistical analysis for human samples compared results from PE vs. normal controls. Researchers were blinded to disease state until after analysis was complete. Forty patients were enrolled in the study: 20 had normal pregnancies, and 20 had pregnancies complicated by PE. A significant difference (p < 0.005) was found in gestational age at birth between groups. Pre‐eclampsia was associated with larger overall microvessel caliber, diminished capillary size for microvasculature associated with pericytes, and diminished pericyte number relative to controls. BMI and smoking status were both inversely correlated with pericyte number. The phenotypic changes observed in placental microvessels from PE pregnancies may be related to placental hypoxia and are associated with modifiable risk factors known to underlie other microvascular diseases.