title: Pulmonary vascular changes 22 years after single lung transplantation for pulmonary arterial hypertension: a case report with molecular and pathological analysis.
abstract: This study was undertaken to characterize the molecular and pathological mechanisms of pulmonary vascular remodeling in a patient who developed chronic lung allograft dysfunction and recurrent pulmonary hypertension (PH) 22 years after undergoing a right single lung transplantation for pulmonary arterial hypertension (PAH). Histopathologic examination of the explanted lungs at the time of retransplantation showed characteristics of diffuse vascular remodeling combined with features of acute and chronic thromboemboli and evidence of bronchiolitis obliterans in the right lung allograft. In contrast, the native left lung demonstrated pulmonary arterial changes in keeping with PAH associated with disseminated pulmonary ossification. Real-time polymerase chain reaction and Western blot-performed on the first lung allograft, the native lung, and the new donor lung-demonstrated increased expression of apoptotic-related gene and protein levels in the lung allograft compared with the native PAH lung and the donor lung. Localization of cell apoptosis determined by triple immunostaining for caspase 3, CD31, and smooth muscle actin was positive in the pulmonary endothelial cells but not the smooth muscle cells of the lung allograft, while no positive staining was detected for cell death in the native PAH lung. The presence of PH in the lung allograft 22 years after transplantation was associated with upregulation of apoptotic markers and evidence of apoptotic endothelial cell death compared with the native lung and donor lung.
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Yidan D
authors.initials: YD
authors.lastname: Zhao
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Peng
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Elise
authors.initials: E
authors.lastname: Granton
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lin
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lu
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Licun
authors.initials: L
authors.lastname: Wu
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Tiago
authors.initials: T
authors.lastname: Machuca
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
keywords: apoptosis; proliferation; pulmonary hypertension; reoccurrence