scholarly journals The Role of Regulatory T Cells in Pulmonary Arterial Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Tian ◽  
Shirley Y. Jiang ◽  
Xinguo Jiang ◽  
Rasa Tamosiuniene ◽  
Dongeon Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Pulmonary Arterial Hypertension ◽  
Regulatory T Cells ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Strongly Correlated ◽  
Incurable Condition ◽  
Pulmonary Arterial ◽  
Inflammatory Milieu

Pulmonary arterial hypertension (PAH) is a chronic, incurable condition characterized by pulmonary vascular remodeling, perivascular inflammation, and right heart failure. Regulatory T cells (Tregs) stave off autoimmunity, and there is increasing evidence for their compromised activity in the inflammatory milieu of PAH. Abnormal Treg function is strongly correlated with a predisposition to PAH in animals and patients. Athymic Treg-depleted rats treated with SU5416, an agent causing pulmonary vascular injury, develop PAH, which is prevented by infusing missing CD4+CD25highFOXP3+ Tregs. Abnormal Treg activity may also explain why PAH disproportionately affects women more than men. This mini review focuses on the role of Tregs in PAH with a special view to sexual dimorphism and the future promise of Treg therapy.

scholarly journals The Role of Regulatory T Cells in Pulmonary Arterial Hypertension

2019 ◽  
Vol 8 (23) ◽  
Author(s):  
Haihua Qiu ◽  
Yi He ◽  
Fan Ouyang ◽  
Ping Jiang ◽  
Shuhong Guo ◽  
...  
Keyword(s):  
T Cells ◽  
Pulmonary Arterial Hypertension ◽  
Regulatory T Cells ◽  
Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for Pulmonary Arterial Hypertension

2020 ◽  
pp. 1902061
Author(s):  
David Macias ◽  
Stephen Moore ◽  
Alexi Crosby ◽  
Mark Southwood ◽  
Xinlin Du ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Target Genes ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Pulmonary Arterial ◽  
The Impact

Pulmonary Arterial Hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant HIF2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades.Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from IPAH patients were used to determine the impact of HIF2α-inhibition on endothelial function.Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyper-proliferative phenotype and over-active arginase activity in blood outgrowth endothelial cells from IPAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population.

scholarly journals Echocardiography in Pulmonary Arterial Hypertension: Is It Time to Reconsider Its Prognostic Utility?

2021 ◽  
Vol 10 (13) ◽  
pp. 2826
Author(s):  
Ioannis T. Farmakis ◽  
Eftychia Demerouti ◽  
Panagiotis Karyofyllis ◽  
George Karatasakis ◽  
Maria Stratinaki ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Right Heart ◽  
Prognostic Utility ◽  
Pulmonary Arterial ◽  
Prognostic Implications ◽  
The Right

Pulmonary arterial hypertension (PAH) is characterized by an insult in the pulmonary vasculature, with subsequent right ventricular (RV) adaptation to the increased afterload that ultimately leads to RV failure. The awareness of the importance of RV function in PAH has increased considerably because right heart failure is the predominant cause of death in PAH patients. Given its wide availability and reduced cost, echocardiography is of paramount importance in the evaluation of the right heart in PAH. Several echocardiographic parameters have been shown to have prognostic implications in PAH; however, the role of echocardiography in the risk assessment of the PAH patient is limited under the current guidelines. This review discusses the echocardiographic evaluation of the RV in PAH and during therapy, and its prognostic implications, as well as the potential significant role of repeated echocardiographic assessment in the follow-up of patients with PAH.

scholarly journals The role of nuclear factor of activated T cells in pulmonary arterial hypertension

Cell Cycle ◽  
2017 ◽  
Vol 16 (6) ◽  
pp. 508-514 ◽  
Author(s):  
Rui Chen ◽  
Jinchuan Yan ◽  
Peijing Liu ◽  
Zhongqun Wang ◽  
Cuiping Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Pulmonary Arterial

scholarly journals New mechanisms of pulmonary arterial hypertension: role of Ca2+ signaling

2012 ◽  
Vol 302 (8) ◽  
pp. H1546-H1562 ◽  
Author(s):  
Frank K. Kuhr ◽  
Kimberly A. Smith ◽  
Michael Y. Song ◽  
Irena Levitan ◽  
Jason X-J. Yuan
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Right Heart Failure ◽  
Altered Expression ◽  
Pulmonary Vascular Remodeling ◽  
Advanced Stages ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a severe and progressive disease that usually culminates in right heart failure and death if left untreated. Although there have been substantial improvements in our understanding and significant advances in the management of this disease, there is a grim prognosis for patients in the advanced stages of PAH. A major cause of PAH is increased pulmonary vascular resistance, which results from sustained vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness. In addition to other signal transduction pathways, Ca2+ signaling in pulmonary artery smooth muscle cells (PASMCs) plays a central role in the development and progression of PAH because of its involvement in both vasoconstriction, through its pivotal effect of PASMC contraction, and vascular remodeling, through its stimulatory effect on PASMC proliferation. Altered expression, function, and regulation of ion channels and transporters in PASMCs contribute to an increased cytosolic Ca2+ concentration and enhanced Ca2+ signaling in patients with PAH. This review will focus on the potential pathogenic role of Ca2+ mobilization, regulation, and signaling in the development and progression of PAH.

scholarly journals Selection of Infusion Prostacyclin Therapy in Pulmonary Arterial Hypertension: Not Just a Last Resort

2017 ◽  
Vol 16 (1) ◽  
pp. 14-19
Author(s):  
Robert Schilz ◽  
Myung Park
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Survival Advantage ◽  
Right Heart ◽  
Apparent Paradox ◽  
Early Evidence ◽  
Pulmonary Arterial ◽  
Selection Of

Pulmonary arterial hypertension (PAH) is a progressive, fatal vasculopathy that clinically manifests as increased pulmonary vascular resistance and elevation of pulmonary arterial pressures, ultimately leading to right heart failure and death. Median untreated survival period is 2.8 years, with a survival rate of 34% at 5 years before the availability of epoprostenol.1 Parenteral prostacyclin therapy is arguably the most effective and longest Food and Drug Administration-approved class of drugs for PAH and has been included in guidelines for treatment of PAH for almost 20 years. Intravenous epoprostenol as Flolan® remains the only drug that has demonstrated a survival advantage (Figure 1).2 Despite this demonstration of survival advantage and early evidence in its ability to improve a majority (70%) of patients to a point where they no longer required active listing for lung transplantation,3 epoprostenol or other infusion agents have consistently been shown to be withheld or underutilized in patients with advanced PAH.45 This apparent paradox as well as significant successful prostacyclin therapy in a variety of PAH patients6–8 forms the basis of our discussion on the role of infusion prostacyclins in modern management of PAH.

Sign in / Sign up

Export Citation Format

Share Document