scholarly journals Tumor Necrosis Factor Induces Obliterative Pulmonary Vascular Disease in a Novel Model of Connective Tissue Disease–Associated Pulmonary Arterial Hypertension

2020 ◽  
Vol 72 (10) ◽  
pp. 1759-1770 ◽  
Author(s):  
Richard D. Bell ◽  
R. James White ◽  
Maria L. Garcia‐Hernandez ◽  
Emily Wu ◽  
Homaira Rahimi ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tumor Necrosis Factor ◽  
Connective Tissue ◽  
Arterial Hypertension ◽  
Vascular Disease ◽  
Tumor Necrosis ◽  
Pulmonary Vascular Disease ◽  
Pulmonary Arterial ◽  
Novel Model ◽  
Necrosis Factor

MicroRNA‐140‐5p targeting tumor necrosis factor‐α prevents pulmonary arterial hypertension

2018 ◽  
Vol 234 (6) ◽  
pp. 9535-9550 ◽  
Author(s):  
Tian‐Tian Zhu ◽  
Wei‐Fang Zhang ◽  
Ya‐Ling Yin ◽  
Yu‐Hao Liu ◽  
Ping Song ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tumor Necrosis Factor ◽  
Arterial Hypertension ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Pulmonary Arterial ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals TIFA protein expression is associated with pulmonary arterial hypertension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao-Chih Chang ◽  
Tong-You Wade Wei ◽  
Pei-Yu Wu ◽  
Ming-Daw Tsai ◽  
Wen-Chung Yu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tumor Necrosis Factor ◽  
Protein Expression ◽  
Arterial Hypertension ◽  
Tumor Necrosis ◽  
Heart Catheterization ◽  
Cellular Expression ◽  
Tnf Α ◽  
Pulmonary Arterial ◽  
Necrosis Factor

AbstractTumor 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.

scholarly journals TIFA Protein Expression is Associated with Pulmonary Arterial Hypertension

2021 ◽  
Author(s):  
Hao-Chih Chang ◽  
Tong-You Wade Wei ◽  
Pei-Yu Wu ◽  
Ming-Daw Tsai ◽  
Wen-Chung Yu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tumor Necrosis Factor ◽  
Protein Expression ◽  
Arterial Hypertension ◽  
Tumor Necrosis ◽  
Heart Catheterization ◽  
Cellular Expression ◽  
Tnf Α ◽  
Pulmonary Arterial ◽  
Necrosis Factor

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.

scholarly journals Telangiectases in Scleroderma: A Potential Clinical Marker of Pulmonary Arterial Hypertension

2009 ◽  
Vol 37 (1) ◽  
pp. 98-104 ◽  
Author(s):  
AMI A. SHAH ◽  
FREDRICK M. WIGLEY ◽  
LAURA K. HUMMERS
Keyword(s):  
Regression Analysis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Disease ◽  
Pulmonary Vascular Disease ◽  
Early Therapy ◽  
Clinical Marker ◽  
Point Increase ◽  
Pulmonary Arterial ◽  
The Mean

Objective.Clinical markers are needed to identify scleroderma patients at risk for pulmonary arterial hypertension (PAH) since early therapy may improve survival. We investigated whether increased numbers of telangiectases in scleroderma associate with measures of pulmonary vascular disease.Methods.One hundred forty-seven consecutive adult patients with scleroderma were enrolled in this cross-sectional study and scored for the presence of matted telangiectases on 11 body areas. Per body area, telangiectases were scored as 0 if none were present, 1 if there were fewer than 10 telangiectases, and 2 if 10 or more telangiectases were counted. Linear regression analysis was performed to assess the association between right ventricular systolic pressure (RVSP) and telangiectasia score, adjusted for age, race, smoking status, scleroderma subtype, disease duration, and autoantibody status. Logistic regression analysis was performed with PAH by right-heart catheterization (RHC) as the dependent variable.Results.The mean telangiectasia score was 6.0 (SD 4.5, range 0–20). RVSP and telangiectasia score were positively correlated (r = 0.271, p = 0.001). The mean RVSP increased by 10.9 mm Hg for every 10-point increase in telangiectasia score (95% CI 3.6–18.3 mm Hg, p = 0.004), adjusted for potential confounders. The adjusted relative odds of PAH by RHC were 12.4 for patients with a 10-point increase in telangiectasia score (95% CI 1.78–85.9, p = 0.01).Conclusion.Increased numbers of telangiectases strongly associate with the presence of pulmonary vascular disease. Telangiectases may be a clinical marker of more widespread aberrant microvascular disease in scleroderma.

Potential role of exercise echocardiography and right heart catheterization in the detection of early pulmonary vascular disease in patients with systemic sclerosis

2019 ◽  
Vol 4 (3) ◽  
pp. 219-224
Author(s):  
Gabor Kovacs ◽  
Horst Olschewski
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Disease ◽  
Right Heart Catheterization ◽  
Pulmonary Vascular Disease ◽  
Heart Catheterization ◽  
Right Heart ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Arterial

Pulmonary vascular disease represents one of the most frequent complications in systemic sclerosis leading to increased mortality. The recognition and appropriate clinical management of early pulmonary vascular disease could significantly improve the prognosis of affected patients. Early pulmonary vascular disease is characterized by the histological signs of pulmonary vascular remodeling, mildly increased mean pulmonary arterial pressure (21–24 mmHg) at rest, abnormal pulmonary hemodynamics during exercise, decreased exercise capacity, and a high risk for development of pulmonary arterial hypertension. Pulmonary hemodynamics can be investigated during exercise by echocardiography or by right heart catheterization both representing important clinical tools for the screening and confirmation of early pulmonary vascular disease. Further studies are needed to better understand the clinical course of systemic sclerosis patients with early pulmonary vascular disease and to define the characteristics of patients that will or will not profit from pulmonary arterial hypertension treatment.

scholarly journals Cytokines trigger disruption of endothelium barrier function and p38 MAP kinase activation in BMPR2-silenced human lung microvascular endothelial cells

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401988360 ◽  
Author(s):  
Birger Tielemans ◽  
Leanda Stoian ◽  
Rik Gijsbers ◽  
Annelies Michiels ◽  
Allard Wagenaar ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Barrier Function ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Pulmonary Arterial ◽  
Factor Α ◽  
Necrosis Factor

The bone morphogenetic protein receptor II (BMPRII) signaling pathway is impaired in pulmonary arterial hypertension and mutations in the BMPR2 gene have been observed in both heritable and idiopathic pulmonary arterial hypertension. However, all BMPR2 mutation carriers do not develop pulmonary arterial hypertension, and inflammation could trigger the development of the disease in BMPR2 mutation carriers. Circulating levels and/or lung tissue expression of cytokines such as tumor necrosis factor-α or interleukin-18 are elevated in patients with pulmonary arterial hypertension and could be involved in the pathogenesis of pulmonary arterial hypertension. We consequently hypothesized that cytokines could trigger endothelial dysfunction in addition to impaired BMPRII signaling. Our aim was to determine whether impairment of BMPRII signaling might affect endothelium barrier function and adhesiveness to monocytes, in response to cytokines. BMPR2 was silenced in human lung microvascular endothelial cells (HLMVECs) using lentiviral vectors encoding microRNA-based hairpins. Effects of tumor necrosis factor-α and interleukin-18 on HLMVEC adhesiveness to the human monocyte cell line THP-1, adhesion molecule expression, endothelial barrier function and activation of P38MAPK were investigated in vitro. Stable BMPR2 silencing in HLMVECs resulted in impaired endothelial barrier function and constitutive activation of P38MAPK. Adhesiveness of BMPR2-silenced HLMVECs to THP-1 cells was enhanced by tumor necrosis factor-α and interleukin-18 through ICAM-1 adhesion molecule. Interestingly, tumor necrosis factor-α induced activation of P38MAPK and disrupted endothelial barrier function in BMPR2-silenced HLMVECs. Altogether, our findings showed that stable BMPR2 silencing resulted in impaired endothelial barrier function and activation of P38MAPK in HLMVECs. In BMPR2-silenced HLMVECs, cytokines enhanced adhesiveness capacities, activation of P38MAPK and impaired endothelial barrier function suggesting that cytokines could trigger the development of pulmonary arterial hypertension in a context of impaired BMPRII signaling pathway.

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