Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescence of ECs, and those ECs were easily killed by cellular stresses. In contrast, overexpression of VASH1 made ECs resistant to premature senescence and cell death caused by cellular stresses. The synthesis of VASH1 was regulated by HuR-mediated post-transcriptional regulation. We sought to define the underlying mechanism. VASH1 increased the expression of (superoxide dismutase 2) SOD2, an enzyme known to quench reactive oxygen species (ROS). Simultaneously, VASH1 augmented the synthesis of sirtuin 1 (SIRT1), an anti-aging protein, which improved stress tolerance. Paraquat generates ROS and causes organ damage when administered in vivo. More VASH1 (+/−) mice died due to acute lung injury caused by paraquat. Intratracheal administration of an adenovirus vector encoding human VASH1 augmented SOD2 and SIRT1 expression in the lungs and prevented acute lung injury caused by paraquat. Thus, VASH1 is a critical factor that improves the stress tolerance of ECs via the induction of SOD2 and SIRT1.

lung grafts from DCD can experience additional injuries, including aspiration, warm ischemia, hypoxemia, and hypotension (shock lung). Primary graft dysfunction (PGD), which derives from ischemia-reperfusion injury plus other underlying graft injuries, impairs graft quality that, in turn,

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator that activates many antioxidant enzymes. Oxidative stress, which accumulates in diseased lungs associated with pulmonary hypertension (PH), is thought to be responsible for the progression of cardiopulmonary changes. To test whether Nrf2 activation would exert therapeutic efficacy against cardiopulmonary changes in a hypoxia-induced PH model, wild-type (WT) and Nrf2-deficient mice as well as Kelch-like ECH associating protein 1 (Keap1) (negative regulator of Nrf2) knockdown mutant mice were exposed to hypobaric hypoxia for 3 weeks. This chronic hypoxia exacerbated right ventricular systolic pressure, right ventricular hypertrophy (RVH), and pulmonary vascular remodeling in the WT mice. These pathological changes were associated with aberrant accumulation of Tenascin-C, a disease-indicative extracellular glycoprotein. Simultaneous administration of oltipraz, a potent Nrf2 activator, significantly attenuated RVH and pulmonary vascular remodeling and concomitantly ameliorated Tenascin-C accumulation in the hypoxic mice. Hypoxia-exposed Nrf2-deficient mice developed more pronounced RVH than WT mice, whereas hypoxia-exposed Keap1-knockdown mice showed less RVH and pulmonary vascular remodeling than WT mice, underscoring the beneficial potency of Nrf2 activity against PH. We also demonstrated that expression of the Nrf2-regulated antioxidant enzymes was decreased in a patient with chronic obstructive pulmonary disease associated with PH. The decreased antioxidant enzymes may underlie the pathogenesis of cardiopulmonary changes in the patient with chronic obstructive pulmonary disease and PH. The pharmacologically or genetically induced Nrf2 activity clearly decreased RVH and pulmonary vascular remodeling in the hypoxic PH model. The efficacy of oltipraz highlights a promising therapeutic potency of Nrf2 activators for the prevention of PH in patients with hypoxemic lung disease.

Chronic lung allograft dysfunction (CLAD) limits long‐term survival after lung transplant (LT). Ischemia–reperfusion injury (IRI) promotes chronic rejection (CR) and CLAD, but the underlying mechanisms are not well understood. To examine mechanisms linking IRI to CR, a mouse orthotopic LT model using a minor alloantigen strain mismatch (C57BL/10 [B10, H‐2b] → C57BL/6 [B6, H‐2b]) and isograft controls (B6→B6) was used with antecedent minimal or prolonged graft storage. The latter resulted in IRI with subsequent airway and parenchymal fibrosis in prolonged storage allografts but not isografts. This pattern of CR after IRI was associated with the formation of B cell–rich tertiary lymphoid organs within the grafts and circulating autoantibodies. These processes were attenuated by B cell depletion, despite preservation of allograft T cell content. Our observations suggest that IRI may promote B cell recruitment that drives CR after LT. These observations have implications for the mechanisms leading to CLAD after LT.

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Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

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Background As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population. Methods We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan–Meier method was used to model time to death. Results We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579–1056) and 323 days (IQR 129–528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11–4.85). Conclusions In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.