TIFA protein expression is associated with pulmonary arterial hypertension

Abstract Tumor necrosis factor receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA), a key regulator of inflammation, may be involved in the pathogenesis of pulmonary arterial hypertension (PAH). A total of 48 PAH patients (age 50.1 ± 13.1 years, 22.9% men), 25 hyp...

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Autores principales:	Hao-Chih Chang, Tong-You Wade Wei, Pei-Yu Wu, Ming-Daw Tsai, Wen-Chung Yu, Chen-Huan Chen, Shih-Hsien Sung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8f9a9e7f08c4807a4c315981a7a80ff
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spelling	oai:doaj.org-article:f8f9a9e7f08c4807a4c315981a7a80ff2021-12-02T15:40:00ZTIFA protein expression is associated with pulmonary arterial hypertension10.1038/s41598-021-93582-12045-2322https://doaj.org/article/f8f9a9e7f08c4807a4c315981a7a80ff2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93582-1https://doaj.org/toc/2045-2322Abstract Tumor necrosis factor receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA), a key regulator of inflammation, may be involved in the pathogenesis of pulmonary arterial hypertension (PAH). A total of 48 PAH patients (age 50.1 ± 13.1 years, 22.9% men), 25 hypertensive subjects, and 26 healthy controls were enrolled. TIFA protein expression in peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured. Pulmonary arterial hemodynamics were derived from right heart catheterization. PAH patients had the highest expression of TIFA, TNF-α, and IL-1β. TIFA protein expression was significantly associated with IL-1β (r = 0.94; P < 0.001), TNF-α (r = 0.93; P < 0.001), mean pulmonary artery pressure (r = 0.41; P = 0.006), and pulmonary vascular resistance (r = 0.41; P = 0.007). TIFA protein expression could independently predict the presence of PAH (odds ratio [95% confidence interval per-0.1 standard deviation]: 1.72 [1.37–2.16]; P < 0.001) and outperformed echocardiographic estimation. Ex vivo silencing of TIFA protein expression in PBMCs led to the suppression of the cellular expression of IL-1β and TNF-α. IL-1β and TNF-α mediated 80.4% and 56.6% of the causal relationship between TIFA and PAH, respectively, supporting the idea that TIFA protein is involved in the pathogenesis of PAH.Hao-Chih ChangTong-You Wade WeiPei-Yu WuMing-Daw TsaiWen-Chung YuChen-Huan ChenShih-Hsien SungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hao-Chih Chang Tong-You Wade Wei Pei-Yu Wu Ming-Daw Tsai Wen-Chung Yu Chen-Huan Chen Shih-Hsien Sung TIFA protein expression is associated with pulmonary arterial hypertension
description	Abstract Tumor necrosis factor receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA), a key regulator of inflammation, may be involved in the pathogenesis of pulmonary arterial hypertension (PAH). A total of 48 PAH patients (age 50.1 ± 13.1 years, 22.9% men), 25 hypertensive subjects, and 26 healthy controls were enrolled. TIFA protein expression in peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured. Pulmonary arterial hemodynamics were derived from right heart catheterization. PAH patients had the highest expression of TIFA, TNF-α, and IL-1β. TIFA protein expression was significantly associated with IL-1β (r = 0.94; P < 0.001), TNF-α (r = 0.93; P < 0.001), mean pulmonary artery pressure (r = 0.41; P = 0.006), and pulmonary vascular resistance (r = 0.41; P = 0.007). TIFA protein expression could independently predict the presence of PAH (odds ratio [95% confidence interval per-0.1 standard deviation]: 1.72 [1.37–2.16]; P < 0.001) and outperformed echocardiographic estimation. Ex vivo silencing of TIFA protein expression in PBMCs led to the suppression of the cellular expression of IL-1β and TNF-α. IL-1β and TNF-α mediated 80.4% and 56.6% of the causal relationship between TIFA and PAH, respectively, supporting the idea that TIFA protein is involved in the pathogenesis of PAH.
format	article
author	Hao-Chih Chang Tong-You Wade Wei Pei-Yu Wu Ming-Daw Tsai Wen-Chung Yu Chen-Huan Chen Shih-Hsien Sung
author_facet	Hao-Chih Chang Tong-You Wade Wei Pei-Yu Wu Ming-Daw Tsai Wen-Chung Yu Chen-Huan Chen Shih-Hsien Sung
author_sort	Hao-Chih Chang
title	TIFA protein expression is associated with pulmonary arterial hypertension
title_short	TIFA protein expression is associated with pulmonary arterial hypertension
title_full	TIFA protein expression is associated with pulmonary arterial hypertension
title_fullStr	TIFA protein expression is associated with pulmonary arterial hypertension
title_full_unstemmed	TIFA protein expression is associated with pulmonary arterial hypertension
title_sort	tifa protein expression is associated with pulmonary arterial hypertension
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f8f9a9e7f08c4807a4c315981a7a80ff
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TIFA protein expression is associated with pulmonary arterial hypertension

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