Abstract:
:Quantifying metabolic derangements in pulmonary hypertension (PH) by plasma metabolomics could identify biomarkers useful for diagnosis and treatment. The objective of this paper is to test the hypotheses that circulating metabolites are differentially expressed in PH patients compared with controls and among different hemodynamic subtypes of PH associated with left heart disease. We studied patients enrolled in the CATHGEN biorepository with PH (right heart catheterization mPAP ≥ 25 mmHg; n = 280). Of these, 133 met criteria for postcapillary PH, 82 for combined precapillary and postcapillary PH (CpcPH), and 65 for precapillary PH. Targeted profiling of 63 metabolites (acylcarnitines, amino acids, and ketones) was performed using tandem flow injection mass spectrometry. Multivariable linear regression was used to determine differences in metabolite factors derived from a principal components analysis between PH cases, PH subtypes, and non-PH controls. In adjusted models, the metabolite factor loaded with long-chain acylcarnitines was higher in all PH cases versus non-PH controls (P = 0.00008), but did not discriminate between CpcPH and postcapillary PH (P = 0.56). In analyses of subtypes, CpcPH patients had lower levels of factors loaded with urea cycle amino acids and short chain acylcarnitines as compared to controls (P = 0.002 and P = 0.01, respectively) and as compared to postcapillary PH (P = 0.04 and P = 0.02, respectively). Compared to controls, PH was strongly associated with greater concentrations of long-chain acylcarnitines. Postcapillary PH and CpcPH were weakly associated with distinct metabolomic profiles. These findings suggest the presence of unique metabolic abnormalities in subtypes of PH and may reflect underlying pathophysiology.
journal_name
Pulm Circjournal_title
Pulmonary circulationauthors
Luo N,Craig D,Ilkayeva O,Muehlbauer M,Kraus WE,Newgard CB,Shah SH,Rajagopal Sdoi
10.1086/690554subject
Has Abstractpub_date
2017-02-01 00:00:00pages
211-218issue
1eissn
2045-8932issn
2045-8940pii
10.1086_690554journal_volume
7pub_type
杂志文章abstract::A loss of K+ efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca2+-activated (BK) channels represents a therapeutic strategy to restore K+ efflux to the affected PASMCs. However,...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688838
更新日期:2016-12-01 00:00:00
abstract::Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/689906
更新日期:2017-07-01 00:00:00
abstract::To shed light on the efficacy of oxygen therapy in pulmonary arterial hypertension (PAH) when hypoxemia is not present, we report seven years of observational data for a female patient recorded between February 2012 and February 2019 when she was aged 7.8-14.8 years. The patient was born with an atrial septal defect (...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019845610
更新日期:2019-04-01 00:00:00
abstract::The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow m...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020919355
更新日期:2020-05-14 00:00:00
abstract::Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019851000
更新日期:2019-04-01 00:00:00
abstract::We aimed to evaluate the association between the presence of histologic chorioamnionitis (HC) and development of pulmonary hypertension (PH) during neonatal intensive care unit (NICU) stay. Data of preterm infants born at 32 weeks of gestation or less were reviewed. The development of PH and other respiratory outcomes...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018760166
更新日期:2018-04-01 00:00:00
abstract::Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and h...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/678510
更新日期:2014-12-01 00:00:00
abstract::Echocardiography, a non-invasive and cost-effective method for monitoring cardiac function, is commonly used for evaluation and pre-clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) fun...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019841987
更新日期:2019-04-01 00:00:00
abstract::Limited data about the long-term prognosis and response to therapy in pulmonary arterial hypertension patients with World Health Organization functional class I/II symptoms are available. PubMed and Embase were searched for publications of observational registries and randomized, controlled trials in pulmonary arteria...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020935291
更新日期:2020-11-25 00:00:00
abstract::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 i...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018824564
更新日期:2019-04-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clin...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217705891
更新日期:2017-04-01 00:00:00
abstract::Optimal pulmonary hypertension (PH) management relies on a timely, accurate diagnosis and follow-up in specialized clinics by multidisciplinary teams that have clearly defined responsibilities and protocols. Internationally agreed criteria for expert center staff are lacking, particularly with respect to nurses, who o...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019855611
更新日期:2019-04-01 00:00:00
abstract::In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiograp...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/682221
更新日期:2015-09-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that thi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217710224
更新日期:2017-07-01 00:00:00
abstract::Acute respiratory distress syndrome in patients with Coronavirus disease 19 is associated with an unusually high incidence of pulmonary embolism and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19-associated acute respiratory distr...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020973906
更新日期:2020-12-15 00:00:00
abstract::This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by co...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.87309
更新日期:2011-07-01 00:00:00
abstract::There are limited data on the management of pulmonary arterial hypertension (PAH) in the elderly; therefore, this analysis compared the safety and efficacy of tadalafil between patients ≥65 and <65 years old. This was a post hoc analysis of the randomized, double-blind, placebo-controlled phase 3 Pulmonary Arterial Hy...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674901
更新日期:2014-03-01 00:00:00
abstract::The diagnosis of pulmonary vascular disease (PVD) is usually based on hemodynamic and/or clinical criteria. Noninvasive imaging of the heart and proximal vasculature can also provide useful information. An alternate approach to such criteria in the diagnosis of PVD is to image the vascular abnormalities in the lungs t...
journal_title:Pulmonary circulation
pub_type:
doi:10.1086/685110
更新日期:2016-03-01 00:00:00
abstract::This manuscript on endpoints incorporates the broad experience of members of Pulmonary Vascular Research Institute's Innovative Drug Development Initiative as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertens...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020962960
更新日期:2020-11-18 00:00:00
abstract::Right ventricular failure (RVF) is the most important prognostic factor for both morbidity and mortality in pulmonary arterial hypertension (PAH), but also occurs in numerous other common diseases and conditions, including left ventricle dysfunction. RVF remains understudied compared with left ventricular failure (LVF...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217714463
更新日期:2017-07-01 00:00:00
abstract::Cardiac magnetic resonance-derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019897513
更新日期:2020-02-10 00:00:00
abstract::Microparticle release by vascular endothelium has been implicated in various cardiovascular pathologies. Ventilator-induced lung injury (VILI) is a life-threatening complication of mechanical ventilation at high tidal volumes associated with excessive mechanical stretch of pulmonary vascular endothelial cells. However...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.109921
更新日期:2013-01-01 00:00:00
abstract::Carboxyl terminus of Hsc70-interacting protein (CHIP) is a 35-kDa cytoplasmic protein expressed in human striated muscle, brain, aortic smooth muscle, endothelial cells, and other tissues. Studies have confirmed that CHIP regulates cell growth, apoptosis, cell phenotype, metabolism, neurodegeneration, etc. However, wh...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019875343
更新日期:2019-09-09 00:00:00
abstract::Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the poten...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688314
更新日期:2016-12-01 00:00:00
abstract::Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geome...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018800439
更新日期:2018-10-01 00:00:00
abstract::We hypothesized that vibrations created by the pulmonary circulation would create sound like the vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) might have a unique sound signature. We recorded heart sounds at the cardiac apex and the second left intercostal space (2LICS), using a ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/683694
更新日期:2015-12-01 00:00:00
abstract::Pulmonary hypertension (PH) comprises a group of pathophysiological syndromes characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, which lead to right ventricular overload, and even right heart failure. PH has a poor prognosis and severely leads to a decline in quality of life. Histor...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020937129
更新日期:2020-07-07 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo-A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo-A1 are related to dysregulation of the ubiquitin-proteasome pathway (UPP). Of 36 recruited pa...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674763
更新日期:2013-12-01 00:00:00
abstract::Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real-world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare cos...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019880086
更新日期:2020-03-18 00:00:00
abstract::Uncorrected atrial septal defect undergoes right ventricle chronic volume overload which may lead to pulmonary hypertension and Eisenmenger Syndrome. The soluble suppression of tumorigenicity-2 is a left ventricle strain biomarker; however, its role in right ventricle strain is unclear. This study aimed to investigate...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020915832
更新日期:2020-05-26 00:00:00