Mechanisms underlying the roles of leukocytes in the progression of cystic fibrosis

Recent advances in cystic fibrosis (CF) treatments have led to improved survival, with life expectancy for Australians living with CF at 57yo. As life expectancy improves, long-term cardiovascular disease risk factors (as for the general population) will become an issue in these patients. We hypothe...

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Published in:Experimental lung research 2024-12, Vol.50 (1), p.208-220
Main Authors: Asare, Patrick F, Jayapal, Minnu, Tai, Andrew, Maiolo, Suzanne, Chapman, Sally, Morton, Judith, Hopkins, Emily, Reynolds, Paul N, Hodge, Sandra, Tran, Hai Bac
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container_title Experimental lung research
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creator Asare, Patrick F
Jayapal, Minnu
Tai, Andrew
Maiolo, Suzanne
Chapman, Sally
Morton, Judith
Hopkins, Emily
Reynolds, Paul N
Hodge, Sandra
Tran, Hai Bac
description Recent advances in cystic fibrosis (CF) treatments have led to improved survival, with life expectancy for Australians living with CF at 57yo. As life expectancy improves, long-term cardiovascular disease risk factors (as for the general population) will become an issue in these patients. We hypothesized that increased leukocyte expression of vasoconstriction and pro-fibrotic mediators may contribute to CF severity in adults with CF. We recruited 13 adult and 24 pediatric healthy controls, and 53 adults and 9 children living with CF. Leukocyte expression/release of endothelin-1 (ET1) and members of the TGF-β/Smad signaling were measured by multifluorescence quantitative confocal microscopy, Western blotting, ELISA, and real-time quantitative polymerase chain reaction. The association between plasma ET1 levels and lung function was assessed. Leukocytes from adults living with CF expressed higher ET1 levels (  = 0.0033), and TGF-β (  = 0.0031); the phosphorylation ratio increased for Smad2/3 (  = 0.0136) but decreased for Smad1/5/8 (  = 0.0007), vs. control subjects. Plasma ET1 levels were significantly increased in adults with CF with FEV
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Plasma ET1 levels were significantly increased in adults with CF with FEV &lt;50% (  = 0.002) vs. controls, and adults with CF with normal lung function. The release of ET1 in adult plasma inversely correlated with CF severity (-0.609,  = 0.046). 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title Mechanisms underlying the roles of leukocytes in the progression of cystic fibrosis
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