Special Issue "Pulmonary Arterial Hypertension (PAH)"

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A special issue of Diseases (ISSN 2079-9721). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (15 February 2014)

Special Issue Editor

Guest Editor
Dr. Allan Lawrie (Website)

Department of Cardiovascular Science, University of Sheffield, UK
Interests: pathobiology of PAH; biomarkers; disease models; inflammatory mechanisms; apoptosis; autophagy

Special Issue Information

Dear Colleagues,

Pulmonary arterial hypertension (PAH) is a rare but devastating disease that carries a terrible prognosis. Pathologically PAH is characterized by sustained vasoconstriction and progressive obliteration of small resistance pulmonary arteries. Current treatments target the sustained vasoconstriction but the prognosis remains poor. There is currently limited information on biomarkers that indicate a patient response to these therapies. There is also an unmet need to develop new treatments that specifically target the progressive vasculopathy in these patients.

This Special Issue will provide an Open Access opportunity to publish research work and review articles related to the novel biomarkers, new molecular insights and potential therapeutic targets.

Dr. Allan Lawrie
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diseases is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


Keywords

  • pulmonary arterial hypertension (PAH)
  • pathobiology
  • biomarkers
  • disease models
  • inflammatory mechanisms
  • apoptosis
  • autophagy

Published Papers (5 papers)

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Research

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Open AccessArticle TRAIL Deficient Mice Are Protected from Sugen/Hypoxia Induced Pulmonary Arterial Hypertension
Diseases 2014, 2(3), 260-273; doi:10.3390/diseases2030260
Received: 11 March 2014 / Revised: 15 July 2014 / Accepted: 28 July 2014 / Published: 31 July 2014
Cited by 1 | PDF Full-text (2592 KB) | HTML Full-text | XML Full-text
Abstract
Pulmonary arterial hypertension (PAH) is a progressive lung disease diagnosed by an increase in pulmonary arterial blood pressure that is driven by a progressive vascular remodelling of small pulmonary arterioles. We have previously reported that tumor necrosis factor apoptosis-inducing ligand (TRAIL) protein [...] Read more.
Pulmonary arterial hypertension (PAH) is a progressive lung disease diagnosed by an increase in pulmonary arterial blood pressure that is driven by a progressive vascular remodelling of small pulmonary arterioles. We have previously reported that tumor necrosis factor apoptosis-inducing ligand (TRAIL) protein expression is increased in pulmonary vascular lesions and pulmonary artery smooth muscle cells (PASMC) of patients with idiopathic PAH. The addition of recombinant TRAIL induces the proliferation and migration of PASMCs in vitro. TRAIL is required for hypoxia-induced pulmonary hypertension in mice, and blockade of TRAIL prevents and reduces disease development in other rodent models of PAH. Due to the availability of knockout and transgenic mice, murine models of disease are key to further advances in understanding the complex and heterogeneous pathogenesis of PAH. However, murine models vary in their disease severity, and are often criticized for lacking the proliferative pulmonary vascular lesions characteristic of PAH. The murine Sugen-hypoxic (SuHx) mouse model has recently been reported to have a more severe PAH phenotype consisting advanced pulmonary vascular remodelling. We therefore aimed to determine whether TRAIL was also required for the development of PAH in this model. C57BL/6 and TRAIL−/− mice were exposed to normoxia, Sugen5416 alone, hypoxia or both Sugen5416 and hypoxia (SuHx). We report here that SuHx treated C57BL/6 mice developed more severe PAH than hypoxia alone, and that TRAIL−/− mice were protected from disease development. These data further emphasise the importance of this pathway and support the use of the SuHx mouse model for investigating the importance of potential mediators in PAH pathogenesis. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))
Open AccessArticle NF-κB Activation Exacerbates, but Is not Required for Murine Bmpr2-Related Pulmonary Hypertension
Diseases 2014, 2(2), 148-167; doi:10.3390/diseases2020148
Received: 18 April 2014 / Revised: 20 May 2014 / Accepted: 21 May 2014 / Published: 30 May 2014
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Abstract
Aim: The present study investigates the role of NF-κB in Bmpr2-related pulmonary hypertension (PH) using a murine model of PH with inducible overexpression of a cytoplasmic tail Bmpr2 mutation. Methods and Results: Electrophoretic mobility shift assay for nuclear extracts in Bmpr2R899X [...] Read more.
Aim: The present study investigates the role of NF-κB in Bmpr2-related pulmonary hypertension (PH) using a murine model of PH with inducible overexpression of a cytoplasmic tail Bmpr2 mutation. Methods and Results: Electrophoretic mobility shift assay for nuclear extracts in Bmpr2R899X mouse lung and immunohistochemistry for NF-κB p65 in human PAH lung demonstrate that NF-κB is activated in end-stage disease. Acute inflammation or expression of a constitutively active NF-κB elicits a strong suppression of the BMP pathway in mice inversely correlating to activation of NF-κB targets. However, Bmpr2 mutation does not result in NF-κB activation in early disease development as assessed by luciferase reporter mice. Moreover, Bmpr2 mutant mice in which NF-κB activation is genetically blocked develop PH indistinguishable from that without the block. Finally, delivery of a virus causing NF-κB activation strongly exacerbates development of PH in Bmpr2 mutant mice, associated with increased remodeling. Conclusion: NF-κB activation exacerbates, but is not required for Bmpr2-related PH. Pulmonary vascular-specific activation of NF-κB may be a “second hit” that drives penetrance in heritable PH. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))

Review

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Open AccessReview Right Ventricular Geometry and Function in Pulmonary Hypertension: Non-Invasive Evaluation
Diseases 2014, 2(3), 274-295; doi:10.3390/diseases2030274
Received: 16 May 2014 / Revised: 3 July 2014 / Accepted: 21 July 2014 / Published: 18 September 2014
Cited by 1 | PDF Full-text (481 KB) | HTML Full-text | XML Full-text
Abstract
Pulmonary hypertension (PH) is a rare disease, which still carries a poor prognosis. PH is characterized by a pressure overload on the right ventricle (RV), which develops hypertrophy, followed by a progressive failure. Accordingly, recent evidence showed that RV function has an [...] Read more.
Pulmonary hypertension (PH) is a rare disease, which still carries a poor prognosis. PH is characterized by a pressure overload on the right ventricle (RV), which develops hypertrophy, followed by a progressive failure. Accordingly, recent evidence showed that RV function has an important prognostic role in patients with PH. Echocardiography, cardiac magnetic resonance (CMR), computed tomography, and nuclear imaging allow a non-invasive evaluation of the RV size and function, but only the first two are routinely used in the clinical arena. Some conventional echocardiographic parameters, such as TAPSE (tricuspid anular plane systolic excursion), have demonstrated prognostic value in patients with PH. Moreover, there are some new advanced echo techniques, which can provide a more detailed assessment of RV function. Three-dimensional (3D) echocardiography allows measurement of RV volumes and ejection fraction, and two-dimensional (2D) speckle tracking (STE), allows assessment of RV myocardial mechanics. CMR provides accurate measurement of RV volumes, ejection fraction, and mass and allows the characterization of the RV wall composition by identifying the presence of fibrosis by late gadolinium enhancement. Although CMR seems to hold promise for both initial assessment and follow-up of patients with PH, its main role has been restricted to diagnostic work-up only. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))
Open AccessReview The Significance of Pulmonary Artery Size in Pulmonary Hypertension
Diseases 2014, 2(3), 243-259; doi:10.3390/diseases2030243
Received: 12 June 2014 / Revised: 21 July 2014 / Accepted: 25 July 2014 / Published: 31 July 2014
Cited by 3 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
Pulmonary hypertension (PH) has been found to have significant morbidity and mortality. The treatment of PH has advanced considerably with increasingly more effective and safer options. With an increasing effort to diagnose patients early, non-invasive techniques are often used to screen those [...] Read more.
Pulmonary hypertension (PH) has been found to have significant morbidity and mortality. The treatment of PH has advanced considerably with increasingly more effective and safer options. With an increasing effort to diagnose patients early, non-invasive techniques are often used to screen those patients likely to have PH. Computerized tomography (CT) chest scans are increasingly utilized in the evaluation of patients with exertional dyspnea, including those with suspected PH. The main role of the CT scan is to evaluate for any associated underlying diseases. There have been attempts to address the utility of CT to predict the presence of PH. This article reviews previously published investigations to summarize the relationship between pulmonary artery dimensions and PH to determine both the strength of the correlation and its discriminatory ability for use in clinical practice. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))
Open AccessReview The Role of Exercise Testing in the Modern Management of Pulmonary Arterial Hypertension
Diseases 2014, 2(2), 120-147; doi:10.3390/diseases2020120
Received: 12 April 2014 / Revised: 28 April 2014 / Accepted: 30 April 2014 / Published: 28 May 2014
Cited by 1 | PDF Full-text (555 KB) | HTML Full-text | XML Full-text
Abstract
A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH) but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT) has been used as a primary outcome measure [...] Read more.
A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH) but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT) has been used as a primary outcome measure to enable the licensing of many of the medications used for this condition. Recent reviews have questioned the validity of this test as a surrogate of clinical outcomes. At the same time, other questions are emerging where exercise testing may be the solution. With the rise in understanding of genetic markers of idiopathic PAH (IPAH), the screening of an otherwise healthy population for incipient pulmonary hypertension (PH) will be required. The proliferation in treatment choices and identification of populations with PH where PAH treatment is not indicated, such as left heart and lung disease, requires more definitive differentiation from patients with PAH. There is a continuing question about the existence and clinical relevance of exercise induced PAH as a cause of unexplained dyspnoea and fatigue and as a latent phase of resting PH. This review presents a summary and critical analysis of the current role of exercise testing in PAH and speculates on future trends. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))

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