NF-κB pathway is involved in CRP-induced effects on pulmonary arterial endothelial cells in chronic thromboembolic pulmonary hypertension

2013 ◽  
Vol 305 (12) ◽  
pp. L934-L942 ◽  
Author(s):  
Marijke Wynants ◽  
Leanda Vengethasamy ◽  
Alicja Ronisz ◽  
Bart Meyns ◽  
Marion Delcroix ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Serotonin Receptor ◽  
Molecular Mechanisms ◽  
Inflammatory Marker ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of proximal pulmonary arteries. The cellular and molecular mechanisms underlying the pathogenesis remain incompletely understood, although we recently evidenced the potential involvement of the inflammatory marker C-reactive protein (CRP). We aimed to investigate the intracellular mechanisms induced by CRP in proximal pulmonary arterial endothelial cells (PAEC). PAEC were isolated from vascular material obtained during pulmonary endarterectomy. RNA was extracted from CRP-stimulated PAEC, and first-stand cDNA was generated. A RT2 profiler PCR Array was used to evaluate the expression of 84 key genes related to NF-κB-mediated signal transduction. CRP-induced NF-κB activation was studied. The effects of pyrrolidine-dithio-carbamate ammonium (PDTC), an inhibitor of the NF-κB pathway, were investigated on CRP-induced adhesion of monocytes to PAEC, adhesion molecule expression, endothelin-1 (ET-1), interleukin-6 (IL-6), and von Willebrand factor (vWF) secretion. Compared with nonstimulated PAEC, serotonin receptor 2B was downregulated by 25%, inhibitor of NF-κB kinase subunit epsilon (IKBKE) by 30%, and toll-like receptor-4 and -6 by 18 and 39%, respectively, in CRP-stimulated PAEC. The transcription factor FOS was threefold upregulated. CRP induced RelA/NF-κBp65 phosphorylation. PDTC dose dependently inhibited the adhesion of monocytes to CRP-stimulated PAEC. PDTC also inhibited the CRP-induced expression of ICAM-1 at the surface of PAEC. PDTC impaired the secretion of ET-1 by 18% and tended to inhibit the secretion of IL-6 by CRP-stimulated PAEC by 46%. PDTC did not inhibit the CRP-induced secretion of vWF. These results suggest an involvement of the NF-κB pathway in mediating different effects of CRP on proximal CTEPH-PAEC.

scholarly journals Pathophysiology, incidence, management, and consequences of cardiac arrhythmia in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

2019 ◽  
Vol 9 (1) ◽  
pp. 204589401983489 ◽  
Author(s):  
Meghan M. Cirulis ◽  
John J. Ryan ◽  
Stephen L. Archer
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Outcome Data ◽  
Current Evidence ◽  
Clinical Aspects ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

Arrhythmias are increasingly recognized as serious, end-stage complications of pre-capillary pulmonary hypertension, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Although arrhythmias contribute to symptoms, morbidity, in-hospital mortality, and possibly sudden death in PAH/CTEPH, there remains a paucity of epidemiologic, pathophysiologic, and outcome data to guide management of these patients. This review summarizes the most current evidence on the topic: from the molecular mechanisms driving arrhythmia in the hypertrophied or failing right heart, to the clinical aspects of epidemiology, diagnosis, and management.

Plasma Lp(a) Levels Are Increased in Patients with Chronic Thromboembolic Pulmonary Hypertension

1998 ◽  
Vol 80 (08) ◽  
pp. 231-232 ◽  
Author(s):  
M. Ignatescu ◽  
G. Zorn ◽  
M. Kneussl ◽  
G. Maurer ◽  
I. M. Lang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Vein Thrombosis ◽  
Large Size ◽  
Number Of Patients ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Genetically Determined ◽  
Deep Vein

SummaryChronic thromboembolic pulmonary hypertension (CTEPH) is a disease resulting from the thromboembolic obstruction of the segmental and/or large size pulmonary arteries, subsequently leading to pulmonary arterial hypertension. Incomplete resolution of acute pulmonary emboli and thrombus organization are believed to be important for the development of the disease. Primary pulmonary hypertension (PPH) is a further disease that at present is poorly understood but shows a clinical picture similar to CTEPH. Since lipoprotein(a) [Lp(a)], a genetically determined risk factor for atherosclerosis and thrombosis, has been found increased in plasma of patients with deep vein thrombosis and pulmonary embolism, we measured plasma Lp(a) levels in 40 patients with CTEPH and 50 patients with PPH and compared them to 50 matched controls. The median for Lp(a) plasma levels was significantly higher in CTEPH patients (26.6 mg/dl) than in PPH patients (9.6 mg/dl) and controls (7.2 mg/dl). Increased plasma Lp(a) could, therefore, play a significant role in the mechanisms of ongoing thrombosis and thrombus organization in CTEPH, while its possible role in PPH can be limited to a small number of patients.

scholarly journals Medical management of chronic thromboembolic pulmonary hypertension

2017 ◽  
Vol 26 (143) ◽  
pp. 160107 ◽  
Author(s):  
Joanna Pepke-Zaba ◽  
Hossein-Ardeschir Ghofrani ◽  
Marius M. Hoeper
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Patient Characteristics ◽  
Term Survival ◽  
Thromboembolic Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase Stimulator ◽  
Pulmonary Arterial

Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, organised into fibrotic material that obstructs large pulmonary arteries, and distal small-vessel arteriopathy. Pulmonary endarterectomy (PEA) is the treatment of choice for eligible patients with CTEPH; in expert centres, PEA has low in-hospital mortality rates and excellent long-term survival. Supportive medical therapy consists of lifelong anticoagulation plus diuretics and oxygen, as needed.An important recent advance in medical therapy for CTEPH is the arrival of medical therapies for patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of CTEPH in patients with inoperable disease or with recurrent/persistent pulmonary hypertension after PEA. Clinical trials of this agent have shown improvements in patients' haemodynamics and exercise capacity. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and prostanoids have been used in the treatment of CTEPH, but evidence of benefit is limited. Challenges in the future development of medical therapy for CTEPH include better understanding of the underlying pathology, end-points to monitor the condition's progress, and the optimisation of pulmonary arterial hypertension therapies in relation to diverse patient characteristics and emerging options such as balloon pulmonary angioplasty.

Pulmonary Endarterectomy: Assessment of Operability, Surgical Description, and Post-op Care

2014 ◽  
Vol 12 (4) ◽  
pp. 186-192 ◽  
Author(s):  
David Poch ◽  
Victor Pretorius
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Artery Wedge Pressure ◽  
Pulmonary Endarterectomy ◽  
Pulmonary Thromboendarterectomy ◽  
Thromboembolic Pulmonary Hypertension ◽  
Wedge Pressure

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg in the presence of occlusive thrombi within the pulmonary arteries. Surgical pulmonary thromboendarterectomy (PTE) is considered the best treatment option for CTEPH.

scholarly journals Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension

2013 ◽  
Vol 305 (2) ◽  
pp. H259-H264 ◽  
Author(s):  
Robert V. MacKenzie Ross ◽  
Mark R. Toshner ◽  
Elaine Soon ◽  
Robert Naeije ◽  
Joanna Pepke-Zaba
Keyword(s):  
Pulmonary Hypertension ◽  
Time Constant ◽  
Pulmonary Circulation ◽  
Wave Reflection ◽  
Arterial Compliance ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Left Heart Failure ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Rc Time Constant

This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance ( Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned that increased wave reflection in proximal CTEPH would be another cause of the decreased RC time constant. We conducted a retrospective analysis of invasive pulmonary hemodynamic measurements in IPAH ( n = 78), proximal CTEPH ( n = 91) before (pre) and after (post) pulmonary endarterectomy (PEA), and distal CTEPH ( n = 53). Proximal CTEPH was defined by a postoperative mean pulmonary artery pressure (PAP) of ≤25 mmHg. Outcome measures were the RC time constant, PVR, Ca, and relationship between systolic and mean PAPs. The RC time constant for pre-PEA CTEPH was 0.49 ± 0.11 s compared with post-PEA-CTEPH (0.37 ± 0.11 s, P < 0.0001), IPAH (0.63 ± 0.14 s, P < 0.001), and distal CTEPH (0.55 ± 0.12 s, P < 0.05). A shorter RC time constant was associated with a disproportionate decrease in systolic PAP with respect to mean PAP. We concluded that the pulmonary RC time constant is decreased in proximal CTEPH compared with IPAH, pre- and post-PEA, which may be explained by increased wave reflection but also, importantly, by persistent structural changes after the removal of proximal obstructions. A reduced RC time constant in CTEPH is in accord with a wider pulse pressure and hence greater right ventricular work for a given mean PAP.

scholarly journals EXPRESS: What’s New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts at the 2020 American Thoracic Society International Conference

2021 ◽  
pp. 204589402110407
Author(s):  
Andrew J Sweatt ◽  
Raju Reddy ◽  
Farbod Rahaghi ◽  
Nadine Al-Naamani
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Research ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
American Thoracic Society ◽  
Future Directions ◽  
International Conference ◽  
Metabolic Dysregulation ◽  
Current State ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

In this conference paper, we review the 2020 American Thoracic Society (ATS) International Conference session titled, “What’s New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts”. This virtual mini-symposium took place on October 21, 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.

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