Rahul Kumar, Michael H. Lee, Biruk Kassa, Dara C. Fonseca Balladares, Claudia Mickael, Linda Sanders, Adam Andruska, Maya Kumar, Edda Spiekerkoetter, Angela Bandeira, Kurt R. Stenmark, Rubin M. Tuder, Brian B. Graham
University of California San Francisco. Zuckerberg San Francisco General Hospital. University of Colorado Anschutz Medical Campus. Stanford University. Universidade de Pernambuco.
United States and Brazil
Clinical Science
Clin Sci 2023; 137: 617-631
DOI: 10.1042/CS20220642
Abstract
Background: Pulmonary hypertension (PH) can occur as a complication of schistosomiasis. In humans, schistosomiasis-PH persists despite antihelminthic therapy and parasite eradication. We hypothesized that persistent disease arises as a consequence of exposure repetition.
Methods: Following intraperitoneal sensitization, mice were experimentally exposed to Schistosoma eggs by intravenous injection, either once or three times repeatedly. The phenotype was characterized by right heart catheterization and tissue analysis.
Results: Following intraperitoneal sensitization, a single intravenous Schistosoma egg exposure resulted in a PH phenotype that peaked at 7-14 days, followed by spontaneous resolution. Three sequential exposures resulted in a persistent PH phenotype. Inflammatory cytokines were not significantly different between mice exposed to one or three egg doses, but there was an increase in perivascular fibrosis in those who received three egg doses. Significant perivascular fibrosis was also observed in autopsy specimens from patients who died of this condition.
Conclusions: Repeatedly exposing mice to schistosomiasis causes a persistent PH phenotype, accompanied by perivascular fibrosis. Perivascular fibrosis may contribute to the persistent schistosomiasis-PH observed in humans with this disease.
Category
Class I. Pulmonary Hypertension Associated with Infection
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes