Synchrotron-based three-dimensional imaging combined with molecular biology to cure pulmonary hypertension

Background: Pulmonary hypertension (PH), high blood pressure in the lung, is a lethal condition where curative treatment is lacking. The vasculature in the lung is highly complex with intricate branching patterns and the vascular remodeling in PH has therefore been difficult to understand from 2D sections. We have previously shown that proteoglycans accumulate in diseased vessels of PH patients and that synchrotron-based micro-CT can provide unique imaging of the pulmonary vasculature.

Aim: The overall aim is to decrease mortality and morbidity in PH by use of 3D-imaging combined with other methods to explore pathobiological mechanisms in search of targets for novel therapy. We also aim to find novel biomarkers for pulmonary vascular remodeling, to study the effects of novel therapies and to contribute to improved use of already available treatments.

Workplan: By use of synchrotron-based imaging we have a unique opportunity to decipher the vascular remodeling in PH of different etiologies and can also evaluate the effects of novel therapies. Since the imaging is non-destructive the tissue can subsequently be sectioned and used for histology, immunohistochemistry, in situ hybridization and laser micro-dissection followed by proteomics.

The findings will then be combined to map cellular and molecular events in 3D space, in human tissue as well as in animal models. The applicant works 50% clinically with pediatric PH and transplantation and the group is therefore also involved in registry-based projects and other clinical initiatives like survey-studies and reviews on PH in the setting of heart transplantation and mechanical heart assist devices.

Significance: Four PhD students, a post doc, five medical students and a research nurse are already involved in the projects. A second post doc and a BMA will be recruited. A majority of the group members are clinically active.

Five years from now we hope to know significantly more about the pathophysiology of PH, to have found new therapeutic targets of interest, and to have contributed to improved guidelines and novel biomarkers. Our work may also lead the way for other groups to start using the techniques available at synchrotrons like MAX IV.