54. Cardiac small vessel imaging by light sheet microscopy and micro CT – discovering the missing link between preeclampsia and higher risk for further cardiovascular disease

Abstract

Introduction In preeclampsia, symptoms such as high blood pressure and albuminuria are caused by a state of anti-angiogenic and immune imbalance resulting in severe endothelial dysfunction. The evaluation of smaller vessels is a challenge, but clinically of increasing importance in understanding endothelial dysregulation. Objective We want to examine whether the increased risk for postpartum maternal cardiovascular disease after preeclamptic pregnancy is resultant from microvascular changes in connection with the structural remodeling processes. Methods We compared echocardiographic data from a human cohort with data from our transgenic animal model (hAGTxhRen) after preeclamptic pregnancy. In addition, we investigated cardiac changes in gene (qPCR) and protein expression levels (ELISA, IHC staining) in maternal rats, as well as alterations in microvascular 3D remodeling using Light Sheet Microscopy and Micro CT. Results We were able to show that the echocardiographic changes in our transgenic rat model are comparable to human data. In our rodent model we found maternal structural remodeling involving ventricular hypertrophy, myocardial fibrosis and inflammation at the end of pregnancy. The microvasculature and entire vascular network has been visualized so far only in cleared mouse brains and lymph nodes and partially in adult mouse hearts. Here, we present the 3D network of lectin-labeled blood vessels in cleared adult rat hearts with the analysis of cardiac small vessels with regard to branching points, vessel length and up to a diameter of 6 μm. Discussion Preeclampsia leads to a structural remodeling in maternal hearts as a presumed cause for weakened functionality. Studies are underway to quantify coronary microvascular pathology as a possible missing link between preeclampsia and higher risk for further cardiovascular disease.