Pulmonary arterial hypertension (PAH) is a rare, incurable disease of the lung arteries that leads to premature death. In PAHs, excess scar tissue and vascular thickening occurs in the lung as a result of the increased ‘biomass’ of cells. These changes impede blood flow and damage the heart, but until now the essential biomass features of PAHs were not known. A team led by investigators at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham Healthcare System, in collaboration with Matthew Steinhauser, MD, a metabolism and cellular imaging expert at the University of Pittsburg, and investigators at the University of Vienna, with the goal of better understanding the origins of arterial biomass in Polycyclic aromatic hydrocarbons.
Using an animal model of PAHs, the team applied retinal medicine and advanced molecular imaging tools to identify the chemical building blocks that arterial cells take up and ultimately contribute to vascular occlusion. Using multiisotope imaging mass spectrometry (MIMS) under the guidance of Steinhauser and Christelle Guillermier, PhD, at BWH, researchers can determine the location and abundance of major contributors to biomass, including the amino acid proline and the sugar molecule glucose. Using MIMS, the team visualized proline and glucose tracers injected into the bloodstream of an animal model of PAHs. They saw that arterial cells in the lung used the particles to build up excess scar tissue (including collagen protein), which contributed to the blockage of blood vessels.
“Our study describes the world’s first use of multi-isotope imaging mass spectrometry (MIMS) in the study of lung disease,” said Bradley Wertheim, MD, MD, director of Brigham’s Division of Pulmonary and Critical Medicine. “MIMS is a powerful microscopy tool that produces a ‘molecular snapshot’ that can provide information down to the resolution of a single cell.”
“These findings suggest that the uptake and metabolism of protein precursors may be central to the biology of PAHs. Closer examination of proline and glucose in PAHs may reveal opportunities to inhibit biomass formation, prevent occlusion of lung arteries, and reduce the chance of heart failure,” he said. Co-author Bradley Marron, MD, of Brigham’s Department of Cardiovascular Medicine: Patients with PAH.
Brigham and Women’s Hospital