scholarly journals BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension

2016 ◽  
Vol 48 (6) ◽  
pp. 1668-1681 ◽  
Author(s):  
Maria-Rosa Ghigna ◽  
Christophe Guignabert ◽  
David Montani ◽  
Barbara Girerd ◽  
Xavier Jaïs ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bronchial Artery ◽  
Gene Mutations ◽  
Systemic Circulation ◽  
Systematic Analysis ◽  
Mutation Status ◽  
Mutation Carriers ◽  
Pulmonary Arterial ◽  
The Impact

The impact of bone morphogenetic protein receptor 2 (BMPR2) gene mutations on vascular remodelling in pulmonary arterial hypertension (PAH) is unknown. We sought to identify a histological profile of BMPR2 mutation carriers.Clinical data and lung histology from 44 PAH patients were subjected to systematic analysis and morphometry.Bronchial artery hypertrophy/dilatation and bronchial angiogenesis, as well as muscular remodelling of septal veins were significantly increased in PAH lungs carrying BMPR2 mutations. We found that patients displaying increased bronchial artery remodelling and bronchial microvessel density, irrespective of the mutation status, were more likely to suffer from severe haemoptysis. History of substantial haemoptysis (>50 mL) was significantly more frequent in BMPR2 mutation carriers. 43.5% of BMPR2 mutation carriers, as opposed to 9.5% of noncarriers, displayed singular large fibrovascular lesions, which appear to be closely related to the systemic lung vasculature.Our analysis provides evidence for the involvement of the pulmonary systemic circulation in BMPR2 mutation-related PAH. We show that BMPR2 mutation carriers are more prone to haemoptysis and that haemoptysis is closely correlated to bronchial arterial remodelling and angiogenesis; in turn, pronounced changes in the systemic vasculature correlate with increased pulmonary venous remodelling, creating a distinctive profile in PAH patients harbouring a BMPR2 mutation.

Abstract 10009: Aortic Hemodynamic and Mechanical Properties are Concomitantly Reduced in Pulmonary Arterial Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michal Schafer ◽  
Omid Jazaeri ◽  
Vitaly O Kheyfets ◽  
Kendall S Hunter ◽  
Robin Shandas ◽  
...  
Keyword(s):  
Elastic Modulus ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Thoracic Aorta ◽  
Systemic Circulation ◽  
Left Ventricular ◽  
Pulmonary Vasculature ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Arterial ◽  
The Impact

Introduction: Although pulmonary arterial hypertension (PAH) has significant impact on flow and tissue remodeling in the pulmonary vasculature, previous studies indicate that PAH is also associated with increased stiffness and endothelial dysfunction in the systemic circulation. Alterations in vascular properties of the systemic circulation may have hemodynamic relevance for left ventricular adaptation to PAH. Reduced wall shear stress (WSS) and vascular elastic markers are known manifestations of vascular disease and may provide insight into the vascular behavior of the systemic circulation in PAH. Hypothesis: We hypothesized that WSS and mechanical elasticity are altered in the thoracic aorta in PAH, and that these measures correlate with pulmonary hemodynamics. Methods: As part of a prospective study, 18 patients with PAH and 5 age-matched controls underwent the same day right heart catheterization (RHC) and 4 dimensional flow cardiac magnetic resonance (4D CMR) for computation of WSS in four aortic regions (endovascular landing zones 1 to 4). The aortic capacitance was calculated as the ratio of stroke volume (SV) and pulse pressure (PP). The elastic modulus was defined as the inverse aortic strain divided by PP. The difference in median values was assessed via Wilcoxon ranked sum method and Spearman rho was used for linear regression analysis. Results: The WSS (N/m2) was significantly reduced in all four aortic zones (zone 1: 0.540 vs. 0.800, p = 0.0325; zone 2: 0.424 vs. 0.615, p = 0.0402; zone 3: 0.419 vs. 0.625, p = 0.0250; zone 4: 0.513 vs. 0.794, p = 0.0046). While aortic capacitance (mL/mmHg) was significantly reduced in the PAH subjects (1.82 vs. 5.97, p = 0.008), the elastic modulus (mmHg) was higher (3.52 vs. 8.25, p = < 0.001). The most significant correlation was between the WSS in zone 4 and pulmonary vascular resistance (rho = -0.70, p = 0.006) and mean pulmonary artery pressure (rho = -0.62, p = 0.002). Conclusions: PAH is associated with reduced WSS in the thoracic aorta, suggesting reduced systemic flow conduction in PAH. WSS and mechanical vascular markers may aid in the understanding of the impact of PAH on systemic hemodynamics and tissue mechanics.

scholarly journals HDL Cholesterol as a Marker of Disease Severity and Prognosis in Patients with Pulmonary Arterial Hypertension

2019 ◽  
Vol 20 (14) ◽  
pp. 3514 ◽  
Author(s):  
Kamil Jonas ◽  
Grzegorz Kopeć
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Endothelium ◽  
Pulmonary Circulation ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Systemic Circulation ◽  
Pulmonary Arterial ◽  
The Impact

The impact of high-density lipoprotein (HDL) cholesterol on the development of atherosclerosis and diseases of systemic circulation has been well documented both in experimental and registry studies. Recent discoveries in pulmonary arterial hypertension (PAH) revealed a significant impact of HDL on pulmonary artery vasoreactivity and patients’ prognosis. The vasoprotective activity of HDL primarily involves vascular endothelium that also plays a central role in pulmonary arterial hypertension (PAH) pathobiology. However, the exact mechanism in which this lipoprotein fraction exerts its effect in pulmonary circulation is still under investigation. This paper reviews potential vasoprotective mechanisms of HDL in pulmonary circulation and presents current clinical reports on the role of HDL in PAH patients.

scholarly journals Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 779
Author(s):  
Daria S. Kostyunina ◽  
Paul McLoughlin
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Sex Chromosomes ◽  
Bone Morphogenetic Protein 2 ◽  
Sex Dimorphism ◽  
Pulmonary Arterial ◽  
The Impact

Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.

scholarly journals Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with chronic thromboembolic pulmonary hypertension (CTEPH): a qualitative interview study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Brooke Currie ◽  
Evan Davies ◽  
Amélie Beaudet ◽  
Larissa Stassek ◽  
Leah Kleinman
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Shortness Of Breath ◽  
Response Options ◽  
Qualitative Interview Study ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
The Impact

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients’ lives is needed to optimally assess the impact of the disease and treatment. Objectives This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients’ lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. Methods Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™‘s instructions, items, and response options. Results Participants (N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an “extremely important” symptom, and seven participants rated fatigue as “extremely important.” The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. Conclusions The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.

scholarly journals Compound BMPR2 gene mutations in a malignant variant of idiopathic pulmonary arterial hypertension

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Walter Serra ◽  
Nicola Marziliano ◽  
Domenico Corradi ◽  
Francesca Brigati ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Gene Mutations ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle

2015 ◽  
Vol 46 (3) ◽  
pp. 832-842 ◽  
Author(s):  
Emmy Manders ◽  
Silvia Rain ◽  
Harm-Jan Bogaard ◽  
M. Louis Handoko ◽  
Ger J.M. Stienen ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Exercise Intolerance ◽  
Muscle Dysfunction ◽  
Striated Muscles ◽  
Pulmonary Arterial ◽  
The Right ◽  
The Impact

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.

Pulmonary hypertension genes as major diagnostic tools

ESC CardioMed ◽  
2018 ◽  
pp. 2490-2493
Author(s):  
Mélanie Eyries ◽  
Barbara Girerd ◽  
David Montani ◽  
David-Alexandre Tregouët ◽  
Marc Humbert ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Gene Mutations ◽  
Diagnostic Tools ◽  
Genetic Mutations ◽  
Incomplete Penetrance ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Sporadic Cases ◽  
Pulmonary Arterial

A few genes have been shown to be major predisposing factors for pulmonary hypertension and are responsible for heritable forms of the disease. However, for nearly all genes described, not all mutation carriers develop the disease (autosomal transmission with incomplete penetrance) explaining the presence of genetic mutations in apparently sporadic cases. Beside mutations in major genes (BMPR2 for pulmonary arterial hypertension and EIF2AK4 for recessive heritable pulmonary veno-occlusive disease), other genes have been involved in a very limited number of cases (KCNK3, CAV1, and Smad8). Gene mutations are also been found as part of syndromic diseases (ACVRL1 mutations in hereditary haemorrhagic telangiectasia and TBX4 in small patella syndrome).

scholarly journals Low-grade albuminuria in pulmonary arterial hypertension

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401882456 ◽  
Author(s):  
Nils P. Nickel ◽  
Vinicio A. de Jesus Perez ◽  
Roham T. Zamanian ◽  
Joshua P. Fessel ◽  
Joy D. Cogan ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Dysfunction ◽  
Urinary Albumin ◽  
Low Grade ◽  
Healthy Controls ◽  
Creatinine Ratio ◽  
Poor Outcome ◽  
Mutation Carriers ◽  
Pulmonary Arterial

Low-grade albuminuria, determined by the urinary albumin to creatinine ratio, has been linked to systemic vascular dysfunction and is associated with cardiovascular mortality. Pulmonary arterial hypertension is related to mutations in the bone morphogenetic protein receptor type 2, pulmonary vascular dysfunction and is increasingly recognized as a systemic disease. In a total of 283 patients (two independent cohorts) diagnosed with pulmonary arterial hypertension, 18 unaffected BMPR2 mutation carriers and 68 healthy controls, spot urinary albumin to creatinine ratio and its relationship to demographic, functional, hemodynamic and outcome data were analyzed. Pulmonary arterial hypertension patients and unaffected BMPR2 mutation carriers had significantly elevated urinary albumin to creatinine ratios compared with healthy controls ( P < 0.01; P = 0.04). In pulmonary arterial hypertension patients, the urinary albumin to creatinine ratio was associated with older age, lower six-minute walking distance, elevated levels of C-reactive protein and hemoglobin A1c, but there was no correlation between the urinary albumin to creatinine ratio and hemodynamic variables. Pulmonary arterial hypertension patients with a urinary albumin to creatinine ratio above 10 µg/mg had significantly higher rates of poor outcome ( P < 0.001). This study shows that low-grade albuminuria is prevalent in pulmonary arterial hypertension patients and is associated with poor outcome. This study shows that albuminuria in pulmonary arterial hypertension is associated with systemic inflammation and insulin resistance.

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.

Sign in / Sign up

Export Citation Format

Share Document