Atherosclerosis, Pulmonary Arterial Hypertension and Preeclampsia are conditions associated with defective vascular remodelling. Lymphocytes contribute to vascular remodelling and perhaps the best evidence is Preeclampsia, in which natural killer cells (NK) are thought to play important roles. Indeed, defective NK function results in inadequate uterine spiral arteries remodelling, leading to defective placentation and compromised fetal growth. Despite the evidence that NK cells contribute to the remodelling of uterine spiral arteries, the underlying mechanisms are not clearly defined. We have set up human cellular systems and mouse models to identify and dissect the cellular and molecular mechanisms underlying the cross talk between uterine NK cells and the vasculature, in the context of their microenvironment, which includes other leukocytes, stromal cells and invading fetal trophoblast.
We hypothesise that cytokines and granule contents released by uterine Natural Killer (uNK) cells target the different layers of the vascular wall.
We aim to identify and dissect the cellular and molecular mechanisms underlying the signalling between uNK cells on the one hand and, on the other, endothelial cells, internal elastic lamina, smooth muscle cells and adventitia at different stages of vascular remodelling during pregnancy.
This work will advance our knowledge on the molecular mechanisms underlying NK cell functions in vascular remodelling, thus helping to clarify the pathogenesis of preeclampsia and potentially lead to identify new targetable pathways that can ameliorate cardiovascular diseases.