scholarly journals ORAI Channels as Potential Therapeutic Targets in Pulmonary Hypertension

Physiology ◽  
2018 ◽  
Vol 33 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Baptiste Rode ◽  
Marc A. Bailey ◽  
Roger Marthan ◽  
David J. Beech ◽  
Christelle Guibert
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Pulmonary Artery ◽  
Therapeutic Targets ◽  
Fatal Disease ◽  
Orai Channels

Pulmonary hypertension is a complex and fatal disease that lacks treatments. Its pathophysiology involves pulmonary artery hyperreactivity, endothelial dysfunction, wall remodelling, inflammation, and thrombosis, which could all depend on ORAI Ca2+ channels. We review the knowledge about ORAI channels in pulmonary artery and discuss the interest to target them in the treatment of pulmonary hypertension.

scholarly journals AGE–RAGE Stress in the Pathophysiology of Pulmonary Hypertension and its Treatment

2019 ◽  
Vol 28 (02) ◽  
pp. 071-079 ◽  
Author(s):  
Kailash Prasad
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Heart Diseases ◽  
Therapeutic Targets ◽  
Vascular Hypertrophy ◽  
Soluble Rage ◽  
Glycation End Products ◽  
Rage Expression ◽  
Pathophysiologic Mechanisms ◽  
Group 1

AbstractPulmonary hypertension (PH) is a rare and fatal disease characterized by elevation of pulmonary artery pressure ≥ 25 mm Hg. There are five groups of PH: (1) pulmonary artery (PA) hypertension (PAH), (2) PH due to heart diseases, (3) PH associated with lung diseases/hypoxia, (4) PH associated with chronic obstruction of PA, and (5) PH due to unclear and/or multifactorial mechanisms. The pathophysiologic mechanisms of group 1 have been studied in detail; however, those for groups 2 to 5 are not that well known. PH pathology is characterized by smooth muscle cells (SMC) proliferation, muscularization of peripheral PA, accumulation of extracellular matrix (ECM), plexiform lesions, thromboembolism, and recanalization of thrombi. Advanced glycation end products (AGE) and its receptor (RAGE) and soluble RAGE (sRAGE) appear to be involved in the pathogenesis of PH. AGE and its interaction with RAGE induce vascular hypertrophy through proliferation of vascular SMC, accumulation of ECM, and suppression of apoptosis. Reactive oxygen species (ROS) generated by interaction of AGE and RAGE modulates SMC proliferation, attenuate apoptosis, and constricts PA. Increased stiffness in the artery due to vascular hypertrophy, and vasoconstriction due to ROS resulted in PH. The data also suggest that reduction in consumption and formation of AGE, suppression of RAGE expression, blockage of RAGE ligand binding, elevation of sRAGE levels, and antioxidants may be novel therapeutic targets for prevention, regression, and slowing of progression of PH. In conclusion, AGE–RAGE stress may be involved in the pathogenesis of PH and the therapeutic targets should be the AGE–RAGE axis.

scholarly journals Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction

2009 ◽  
Vol 296 (5) ◽  
pp. H1312-H1320 ◽  
Author(s):  
Roshan P. Weerackody ◽  
David J. Welsh ◽  
Roger M. Wadsworth ◽  
Andrew J. Peacock
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Pulmonary Artery ◽  
P38 Mapk ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Mapk Activity ◽  
Novel Target ◽  
Endothelium Dependent Relaxation

Hypoxia-induced endothelial dysfunction plays a crucial role in the pathogenesis of hypoxic pulmonary hypertension. p38 MAPK expression is increased in the pulmonary artery following hypoxic exposure. Recent evidence suggests that increased p38 MAPK activity is associated with endothelial dysfunction. However, the role of p38 MAPK activation in pulmonary artery endothelial dysfunction is not known. Sprague-Dawley rats were exposed to 2 wk hypobaric hypoxia, which resulted in the development of pulmonary hypertension and vascular remodeling. Endothelium-dependent relaxation of intrapulmonary vessels from hypoxic animals was impaired due to a reduced nitric oxide (NO) generation. This was despite increased endothelial NO synthase immunostaining and protein expression. Hypoxia exposure increased superoxide generation and p38 MAPK expression. The inhibition of p38 MAPK restored endothelium-dependent relaxation, increased bioavailable NO, and reduced superoxide production. In conclusion, the pharmacological inhibition of p38 MAPK was effective in increasing NO generation, reducing superoxide burden, and restoring hypoxia-induced endothelial dysfunction in rats with hypoxia-induced pulmonary hypertension. p38 MAPK may be a novel target for the treatment of pulmonary hypertension.

scholarly journals Pulmonary Hypertension Secondary to COPD

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Adil Shujaat ◽  
Abubakr A. Bajwa ◽  
James D. Cury
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Pulmonary Artery ◽  
Exercise Capacity ◽  
Oxygen Therapy ◽  
Pulmonary Vasodilators ◽  
Increased Risk ◽  
Acute Exacerbations ◽  
Long Term Oxygen Therapy

The development of pulmonary hypertension in COPD adversely affects survival and exercise capacity and is associated with an increased risk of severe acute exacerbations. Unfortunately not all patients with COPD who meet criteria for long term oxygen therapy benefit from it. Even in those who benefit from long term oxygen therapy, such therapy may reverse the elevated pulmonary artery pressure but cannot normalize it. Moreover, the recent discovery of the key roles of endothelial dysfunction and inflammation in the pathogenesis of PH provides the rationale for considering specific pulmonary vasodilators that also possess antiproliferative properties and statins.

Ex Vivo Measurement of Mouse Pulmonary Artery Biomechanics

2002 ◽  
Author(s):  
Naomi C. Chesler ◽  
John A. Thompson-Figueroa ◽  
Kenneth M. Millburne
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Genetic Factor ◽  
Primary Pulmonary Hypertension ◽  
Ex Vivo ◽  
Fatal Disease ◽  
Pulmonary Vascular Remodeling ◽  
Sporadic Cases

Primary pulmonary hypertension (PPH) is a rapidly progressing and often fatal disease that induces substantial pulmonary vascular remodeling [1]. Although a genetic factor has been identified in familial and sporadic cases of pulmonary hypertension [2], the etiology of the disease for most victims remains unknown.

scholarly journals Role of endothelial dysfunction in pathogenesis of pulmonary hypertension in bronchial asthma patients

2008 ◽  
pp. 38-41
Author(s):  
S. A. Boruta ◽  
E. R. Shakhnis ◽  
M. G. Omelyanenko
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Plasma Level ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Bronchial Asthma ◽  
Middle Aged ◽  
Aged Patients ◽  
Artery Pressure

The aim of this work was to investigate a role of endothelial dysfunction for development of pulmonary hypertension in young and middle-aged bronchial asthma (BA) patients. In total, 56 patients with mild and moderate persisting BA were examined. The endothelial function was assessed using nitrate levels in erythrocytes and plasma and L-arginin concentration in plasma. Endothelial dysfunction was more prominent in patients with moderate BA. Severity of endothelial dysfunction correlated to obstructive disorders. Plasma and erythrocytes nitrates and plasma L-arginin concentrations were lower in females than were in males and were lower in middle-aged patients compared to youngs. Endothelial dysfunction was more severe in patients with pulmonary hypertension than were patients with normal pulmonary artery pressure. Correlations were revealed between plasma level of nitrates and pulmonary artery pressure, plasma level of nitrates and the right ventricle size. Therefore, endothelial dysfunction could result in cardiovascular pathology in asthmatic patients.

Pulmonary Embolization in the Dog: Its Effects on Blood Coagulation and on Pulmonary Artery Pressures

1961 ◽  
Vol 06 (01) ◽  
pp. 025-036 ◽  
Author(s):  
James W. Hampton ◽  
William E. Jaques ◽  
Robert M. Bird ◽  
David M. Selby
Keyword(s):  
Pulmonary Hypertension ◽  
Particulate Matter ◽  
Pulmonary Artery ◽  
Amniotic Fluid ◽  
Blood Coagulation ◽  
Glass Beads ◽  
Pulmonary Vessels ◽  
Pulmonary Embolization ◽  
Biological Nature

Summary1. Infusions containing particulate matter, viz. whole amniotic fluid, amniotic fluid sediment, and glass beads, produce in dogs changes in both early and late phases of the clotting reaction. These changes are associated with the development of pulmonary hypertension.2. When dogs were given an active fibrinolysin followed by an infusion of whole amniotic fluid, the alterations in the clotting mechanism were either delayed or did not appear. No pulmonary hypertension developed in these animals.3. We infer that infusions containing particulate matter will produce in dogs both pulmonary hypertension and changes in the clotting mechanism. Although these are independent changes, both are as closely related to the damage to the pulmonary vessels as they are to the biological nature of the infusions.

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.

Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

2013 ◽  
Vol 20 (37) ◽  
pp. 4806-4814 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Rita Businaro ◽  
Luciano Saso ◽  
Raffaele Capoano ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Immune Cell ◽  
Therapeutic Targets ◽  
Immune Cell Activation ◽  
Novel Therapeutic
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