scholarly journals Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension

2020 ◽  
Vol 10 (1) ◽  
pp. 204589402090878
Author(s):  
Nina Denver ◽  
Natalie Z.M. Homer ◽  
Ruth Andrew ◽  
Katie Y. Harvey ◽  
Nicholas Morrell ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arteries ◽  
Metabolite Profile ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Proof Of Concept ◽  
Increased Risk ◽  
Small Cohort ◽  
Pulmonary Arterial ◽  
Estradiol Metabolism

Increased risk and severity of idiopathic pulmonary arterial hypertension (iPAH) is associated with elevated estradiol in men and postmenopausal women. Pulmonary arteries synthesise estradiol via aromatase and metabolise it via CYP1B1 to mitogenic metabolites; SNPs in aromatase and CYP1B1 have been associated with PAH. This suggests that estradiol metabolism could be altered in iPAH. This proof-of-concept study profiles estradiol and several metabolites of estradiol simultaneously in serum from iPAH patients and controls. We show that the estradiol and metabolite profile is altered in iPAH and that 16-hydroxyestrone and 16-hydroxyestradiol accumulate in iPAH patients with 16-hydroxyestrone levels relating to disease severity.

scholarly journals Long-Term Survival in Idiopathic Pulmonary Arterial Hypertension Associated with Massive Pulmonary Artery Dilation

2011 ◽  
Vol 18 (3) ◽  
pp. e50-e51 ◽  
Author(s):  
Vanja Petrovic ◽  
Christopher J Ryerson ◽  
Robert D Levy
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Present Report ◽  
Pulmonary Arteries ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Channel Blockers ◽  
Term Survival ◽  
Long Term Survival ◽  
Pulmonary Arterial

The present report describes two patients with long-term survival after being diagnosed with idiopathic pulmonary arterial hypertension more than 20 years earlier. Both patients were treated with calcium channel blockers for several years and are currently maintained on bosentan, an oral endothelin receptor antagonist. Severe dilation of the main pulmonary arteries is present in both patients and may be related to long-term survival with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension

ESC CardioMed ◽  
2018 ◽  
pp. 2524-2527
Author(s):  
Carlos Jardim ◽  
Luciana K. Morinaga ◽  
Rogério Souza
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arteries ◽  
Rare Condition ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Trigger Factor ◽  
Ventricular Afterload ◽  
Pulmonary Arterial ◽  
Improvement In Survival

Idiopathic pulmonary arterial hypertension is a rare condition characterized by the progressive remodelling of the small pulmonary arteries, increasing right ventricular afterload and consequent failure, in the absence of an identifiable baseline condition or trigger factor. For this, an extensive diagnostic investigation is mandatory, together with invasive haemodynamic measurement, in order to ensure the elevation in the pulmonary artery pressure is associated with a pre-capillary pattern. Three main pathways have been associated with the pathophysiology of idiopathic pulmonary arterial hypertension: the endothelin, nitric oxide, and prostacyclin pathways. The development of specific therapies targeting these pathways has significantly improved survival in the last two decades. Although the disease remains as a relentlessly progressive condition, this improvement in survival was also accompanied by better functional capacity and quality of life, thus completely changing the daily life of patients.

scholarly journals Antithrombotic therapy in patients with pulmonary arterial hypertension

2019 ◽  
Vol 25 (1) ◽  
pp. 25-33 ◽  
Author(s):  
N. S. Goncharova ◽  
М. A. Simakova ◽  
O. M. Moiseeva
Keyword(s):  
Risk Factors ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Prospective Studies ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Pulmonary Arteries ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
The Novel ◽  
Pulmonary Arterial

Histology studies fnd organized thrombi in small pulmonary arteries in 57% patients with idiopathic pulmonary arterial hypertension (PAH). This evidence justifed a rationale for the widespread use of oral anticoagulants (OAK) in patients with PAH of various etiologies. In recent years, the concept of OAK therapy in PAH patients has changed due to the novel data from clinical retrospective and prospective studies involving patients with PAH of various etiologies who have received anticoagulants. The present review discusses possible risk factors for thrombosis and bleeding in patients with PAH, indications, effcacy, and safety of OAK therapy in diverse PAH etiologies.

scholarly journals THE COMPLEXITY OF DIAGNOSING IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION

2018 ◽  
Vol 63 (5) ◽  
pp. 167-171
Author(s):  
D. I. Sadykova ◽  
D. R. Sabirova ◽  
N. V. Kustova ◽  
N. N. Firsova ◽  
G. A. Khusnullina
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Clinical Symptoms ◽  
Pulmonary Arteries ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Incurable Disease ◽  
Pulmonary Arterial ◽  
Unclear Etiology ◽  
High Degree ◽  
Diagnostic Criterion

Idiopathic pulmonary arterial hypertension is a progressive, incurable disease of unclear etiology; it is characterized by intensive remodeling of the pulmonary vascular bed with a predominant lesion of the distal pulmonary arteries and arterioles. A diagnostic criterion of the disease is an increase in the average pressure in the pulmonary artery more than 25 mm Hg. Arterial hypertension is difficult to diagnose, especially at the early stages due to non-specific clinical symptoms. The article describes the clinical case of diagnostics and treatment of a child with primary pulmonary hypertension of high degree.

scholarly journals Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension

2019 ◽  
Vol 53 (6) ◽  
pp. 1800965 ◽  
Author(s):  
Rita Papp ◽  
Chandran Nagaraj ◽  
Diana Zabini ◽  
Bence M. Nagy ◽  
Miklós Lengyel ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Healthy Donor ◽  
Pulmonary Arteries ◽  
Anion Channel ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Systematic Analysis ◽  
Knock Down ◽  
Reverse Remodelling ◽  
Pulmonary Arterial

Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl− channel TMEM16A gene. We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing pulmonary arterial hypertension (PAH).We investigated healthy donor lungs (n=40) and recipient lungs with IPAH (n=38) for the expression of anion channel and transporter genes in small pulmonary arteries and pulmonary artery smooth muscle cells (PASMCs).In IPAH, TMEM16A was strongly upregulated and patch-clamp recordings confirmed an increased Cl− current in PASMCs (n=9–10). These cells were depolarised and could be repolarised by TMEM16A inhibitors or knock-down experiments (n=6–10). Inhibition/knock-down of TMEM16A reduced the proliferation of IPAH-PASMCs (n=6). Conversely, overexpression of TMEM16A in healthy donor PASMCs produced an IPAH-like phenotype. Chronic application of benzbromarone in two independent animal models significantly decreased right ventricular pressure and reversed remodelling of established pulmonary hypertension.Our findings suggest that increased TMEM16A expression and activity comprise an important pathologic mechanism underlying the vasoconstriction and remodelling of pulmonary arteries in PAH. Inhibition of TMEM16A represents a novel therapeutic approach to reverse remodelling in PAH.

scholarly journals Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension

2016 ◽  
Vol 48 (5) ◽  
pp. 1386-1395 ◽  
Author(s):  
Rui Zhang ◽  
Xiao-Jian Wang ◽  
Hong-Da Zhang ◽  
Xiao-Qing Sun ◽  
Qin-Hua Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Prognostic Indicator ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Plasma Metabolites ◽  
Mean Pulmonary Arterial Pressure ◽  
Increased Risk ◽  
Pulmonary Arterial ◽  
The Impact

Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (μmol·L−1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of ≤10 μmol·L−1 had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH.

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