Circulating placenta-secreted glycoproteins and markers of angiogenesis are altered in pregnant women with OSA.

Background: Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. Methods: We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. Results: Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67–2.51) higher risk of mortality compared with non-Black recipients ( P <0.001, interaction P <0.001); however, the risk was significant only in the first year post-transplant (first year: adjusted hazard ratio, 2.30 [95% CI, 1.60–3.31], P <0.001; after first year: adjusted hazard ratio, 0.84 [95% CI, 0.54–1.29]; P =0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25–1.89] P <0.001) and 1.20-fold ([95% CI, 1.09–1.33] P <0.001) higher risk of mortality. Among recipients aged 61 to 80 years, no significant association was seen with Black race (adjusted hazard ratio, 1.12 [95% CI, 0.97–1.29]; P =0.1). Conclusions: Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Apoptosis is a key pathologic feature in acute lung injury. Animal studies have demonstrated that pathways regulating apoptosis are necessary in the development of acute lung injury, and that activation of p38 mitogen-activated protein kinase (MAPK) is linked to the initiation of the apoptotic cascade. In this study, we assessed the role of the MAPK-activated protein kinase (MK) 2, one of p38 MAPK's immediate downstream effectors, in the development of apoptosis in an animal model of LPS-induced pulmonary vascular permeability. Our results indicate that wild-type (WT) mice exposed to LPS demonstrate increased apoptosis, as evidenced by cleavage of caspase 3 and poly (ADP-ribose) polymerase 1 and increased deoxynucleotidyl transferase-mediated dUDP nick-end labeling staining, which is accompanied by increases in markers of vascular permeability. In contrast, MK2 2/2 mice are protected from pulmonary vascular permeability and apoptosis in response to LPS. Although there was no difference in activation of caspase 3 in MK2 2/2 compared with WT mice, interestingly, cleaved caspase 3 translocated to the nucleus in WT mice while it remained in the cytosol of MK2 2/2 mice in response to LPS. In separate experiments, LPS-induced apoptosis in human lung microvascular endothelial cells was also associated with nuclear translocation of cleaved caspase 3 and apoptosis, which were both prevented by MK2 silencing. In conclusion, our data suggest that MK2 plays a critical role in the development of apoptosis and pulmonary vascular permeability, and its effects on apoptosis are in part related to its ability to regulate nuclear translocation of cleaved caspase 3.