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.

Abstract 13855: The Impact of Plasma Levels of Receptor for Advanced Glycation End-products and High Mobility Group Box 1 in Patients With Pulmonary Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Suzuki ◽  
Kazuhiko Nakazato ◽  
Koichi Sugimoto ◽  
Akiomi Yoshihisa ◽  
Takayoshi Yamaki ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Advanced Glycation End Products ◽  
Plasma Levels ◽  
High Mobility ◽  
High Mobility Group ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Background: In pulmonary hypertension (PH), the increase of pulmonary artery pressure by vasoconstriction, remodeling of small pulmonary arteries, and chronic pulmonary thromboembolism result in right ventricular failure and ultimately death. Nuclear protein, high mobility group box 1 (HMGB1), stabilizes nucleosome, and on release into extracellular environment, HMGB1 acts as a pro-inflammatory cytokine by activating pattern recognition receptors including receptor for advanced glycation end-products (RAGE). HMGB1 is one of endogenous ligands of RAGE, and HMGB1 and RAGE are ubiquitously expressed in various organs. Several reports have recently revealed that RAGE is expressed in pulmonary artery in patients with PH, and HMGB1 contributes to migration of vascular smooth muscle cells in PH patient. The purpose of this study was to examine the clinical significance of circulating levels of HMGB1 and RAGE in patients with PH. Methods and Results: Plasma levels of HMGB1 and soluble RAGE were measured in 33 patients with PH (9 in idiopathic PH, 7 in PH related to collagen disease, 9 in chronic thromboembolic PH (CTEPH), 8 in others) and 30 normal subjects as control. Plasma levels of HMGB1 were not difference between PH patients and control subjects, however, plasma levels of soluble RAGE were significantly higher in patients with PH than in control (1464.2 vs. 831.7 pg/ml, P=0.008). Plasma soluble RAGE levels were higher in idiopathic PH (P<0.001), PH related to collagen disease (P=0.050), and CTEPH (P=0.002) than control. In addition, there was statistically significant positive correlation between pressure gradient of tricuspid valve and plasma level of soluble RAGE (R=0.403, P=0.019). Conclusions: Plasma levels of soluble RAGE, but not HMGB1, might be a novel marker which reflects the pathological conditions in patients with PH.

scholarly journals Segmental Pulmonary Hypertension in Children with Congenital Heart Disease

Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 492
Author(s):  
Bibhuti B. Das ◽  
Benjamin Frank ◽  
Dunbar Ivy
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Congenital Heart ◽  
Multimodality Imaging ◽  
Heart Diseases ◽  
Heart Defects ◽  
Pulmonary Atresia ◽  
Pulmonary Vascular Disease ◽  
Variable Degree ◽  
Branch Pulmonary Artery Stenosis

Segmental pulmonary hypertension is a complex condition in children that encompasses many congenital heart diseases including pulmonary atresia with ventricular septal defect, hemitruncus/truncus arteriosus with branch pulmonary artery stenosis, unilateral absent pulmonary artery, and several post-tricuspid shunt lesions. Multimodality imaging is required to confirm and assess pulmonary vascular disease in subjects with major aorto-pulmonary collaterals. We describe 3 children with complex congenital heart defects who have a variable degree of segmental pulmonary hypertension and discuss management strategies and the role of interventional and/or pulmonary hypertension targeted therapies.

scholarly journals Predictors of Chronic Thromboembolic Pulmonary Hypertension

Kardiologiia ◽  
2018 ◽  
Vol 58 (12) ◽  
pp. 60-65
Author(s):  
M. R. Kuznetsov ◽  
I. V. Reshetov ◽  
B. B. Orlov ◽  
A. A. Khotinsky ◽  
A. A. Atayan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Anticoagulant Therapy ◽  
Vena Cava ◽  
Significant Risk ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Pulmonary Hypertension ◽  
Group 2 ◽  
Group 1

Purpose:to elucidate predictors of development of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary artery thromboembolism (PTE).Material and methods. We included in this study 210 patients hospitalized with diagnosis of submassive and massive PTE from 2013 to 2017. In 1 to 3 years after initial hospitalization these patients were invited for control examination. According to results of this examination patients were divided into two groups: with (group 1, n=45) and without (group 2, n=165) signs of CTEPH. Severity of pulmonary artery vascular bed involvement was assessed by multislice computed tomography (MSCT) angiography and lung scintigraphy. For detection of thrombosis in the inferior vena cava system we used ultrasound angioscanning.   Examination also included echocardiography.Results.In the process of mathematical analysis, the following risk factors for the development of CTEPH embolism were determined: duration of thrombotic history (group 1 – 13.70±2.05 days, group 2– 16.16±1.13 days, p=0.015), localization of venous thrombosis in the lower extremities (the most favorable – shin veins, popliteal, and common femoral veins, unfavorable – superficial femoral vein). The choice of the drug for thrombolytic and anticoagulant therapy: streptokinase and urokinase were significantly more effective than alteplase, rivaroxaban was superior to the combination of unfractionated or low molecular weight heparins with warfarin. Also, risk factors for the development of CTEPH were the initial degree of pulmonary hypertension and tricuspid insufficiency, as well as the positive dynamics of these indicators at the background of thrombolytic or anticoagulant therapy. Of concomitant diseases, significant risk factors for development of CTEPH were grade 3 hypertensive disease, diabetes mellitus, post­infarction cardiosclerosis. On the other hand, age, gender, degree of severity at the time of admission, presence of infarction pneumonia, surgical prevention of recurrent pulmonary embolism, number of pregnancies and deliveries, history of trauma and malignancies, cardiac arrhythmias produced no significant impact on the development of CTEPH.

scholarly journals Pulmonary Hypertension in Children with Congenital Left to Right Cardiac Shunt Anomalies

2015 ◽  
Vol 14 (2) ◽  
pp. 31-37
Author(s):  
Chaity Barua ◽  
Sunam Kumar Barua ◽  
Md Zahid Hossain ◽  
Tahmina Karim
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Congenital Heart Diseases ◽  
Age Group ◽  
Cardiac Defects ◽  
Pulmonary Arterial

The Normal Pulmonary Artery (PA) systolic pressure of children and adults is < 30 mm Hg and the mean PA pressure is < 25 mm Hg at sea level. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure > 25 mm Hg at rest or > 30 mm Hg during exercise. An increase in pulmonary flow, vascular resistance, or both can result in pulmonary hypertension. Pulmonary Arterial Hypertension (PAH) commonly arises in patients with Congenital Heart Diseases (CHD) are usually associated with increased pulmonary blood flow. Greater number of patients with Pulmonary Arterial Hypertension (PAH), associated with congenital heart disease, are now surviving into adulthood, many with increasingly complex cardiac defects. Patients with cardiac defects which result in left-to-right shunting tend to develop PAH, owing to the increased shear stress and circumferential stretch induced by pulmonary blood flow, which leads to endothelial dysfunction and progressive vascular remodeling followed by vascular resistance. Pulmonary hypertension in association with congenital heart diseases is seen in large systemicto- pulmonary communications such as Ventricular Septal Defect (VSD), Patent Ductus Arteriosus (PDA) atrioventricular septal defects, aorticopulmonary window defect etc. Pulmonary hypertension associated with large L-R shunt lesions (e.g. VSD, PDA) is called Hyperkinetic Pulmonary Hypertension (PH). It is the result of an increase in pulmonary blood flow, a direct transmission of the systemic pressure to the pulmonary artery, and compensatory pulmonary vasoconstriction. Hyperkinetic PH is usually reversible if the cause is eliminated before permanent changes occur in the pulmonary arterioles. If large L-R shunt lesions are left untreated, irreversible changes take place in the pulmonary vascular bed, with severe pulmonary hypertension and cyanosis due to a reversal of the L-R shunt. This stage is called Eisenmenger syndrome or Pulmonary Vascular Obstructive Disease (PVOD). Surgical correction is not possible at this stage. Due to lack of formal study which of the L-R congenital shunt is more commonly associated with the development of pulmonary hypertension is not known the cross-sectional study therefore intends to find the pattern of congenital L-R heart diseases commonly attributed to the development pulmonary hypertension. The diagnosis of the abovementioned congenital heart disease will be made by echocardiography. In this study, most of the participant [22 (44.0%)] were in the ‘< 1 years’ age group, female were proportionately higher, most patients presented with cough and difficulty in breathing, dyspnoea and tachycardia were the most common clinical findings, murmur mostly systolic were found, Eisenmenger syndrome was not found in any child, ASD was the most common congenital anomaly. About four-fifth of the participants had single congenital anomaly. Two-fifth of the participant was found having severe PAH. Significant correlation were revealed between age group and Pulmonary arterial pressure (R= 0.775), Status of PAH was found significantly different (p< 0.05) in age groups and presence of number of anomalies.Chatt Maa Shi Hosp Med Coll J; Vol.14 (2); Jul 2015; Page 31-37

SO084SILDENAFIL DRUG IN HEMODIALYSIS PATIENTS WITH PULMONARY HYPERTENSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maha Abdelmoneim Behairy Said ◽  
Tamer El Said ◽  
Abdelrahman Elbraky ◽  
Hazem Khorshid ◽  
Waleed Anwar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pulmonary Hypertension ◽  
Placebo Group ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Hemodialysis Patients ◽  
Artery Pressure ◽  
Daily Dose ◽  
Group 2 ◽  
Group 1

Abstract Background and Aims Pulmonary hypertension (PH) is not an uncommon progressive condition in prevalent hemodialysis (HD) patients, associated with high morbidity and mortality. Sildenafil drug has limited studies about the efficacy of the drug and optimal dose among prevalent HD patients with PH. Aim of the study to assess the effects of sildenafil drug on estimated Pulmonary Artery pressure value (ePAP) mmHg via transthoracic Doppler Echocardiography and 6-minute walk test ( 6MWT) among hemodialysis patients with pulmonary hypertension. Method Randomized, double-blind, placebo-controlled clinical trial, from December 2018 to May 2019, involving 60 eligible patients on regular adequate HD with PH, estimated Pulmonary Artery Pressure (ePAP) ≥35 mmHg via Doppler echocardiography. HD patients with mean age 52.6±10.8 year divided randomly into 3 groups: Group 1 (20 patients) received 25 mg sildenafil, group 2 (20 patients) received 50 mg sildenafil and group 3 (20 patients) who received placebo as daily dose treatment for 3 months duration. Every patient in the study was subjected to full history taking and clinical examination. Exclusion Criteria: Current treatment of pulmonary hypertension, patient with evident history of cardiac diseases or chronic pulmonary diseases or systemic autoimmune diseases, portal hypertension, HIV, patients with uncontrolled hypertension or severe anaemia or hypersensitivity to sildenafil, treatment with any drugs that may interact with sildenafil all were excluded from the study. Transthoracic echocardiography was done at the begging of the study and after three months in mid-week non-dialysis day for assessment of the change in ePAP, pulmonary artery pressure calculated using the modified Bernoulli equation, and assessment of right ventricular functions . Exercise capacity assessment by 6MWT to assess the clinical response to the drug, was done for every patient at the start of the study and after 3 months of treatment. Clinically meaningful change estimate for the 6MWT considered as increase more than 30 meters. Results Significant increase in mean of 6 MWT in both group 1,2 received 25 mg,50 mg sildenafil respectively after 3 m duration of treatment versus non-significant change in placebo group as basal 6 MWT was (171 ±45, 214 ±58, 175 ±39) meters in group 1,2 and placebo group respectively (p&gt;0.05). Means 6 MWT post-treatment were (205 ±57, 258 ±59, 182 ±49) meters (P&lt;0.001) in group 1, 2&3 respectively, as post Hoc test results, showed significant increase in 6MWT2 in group 2 in comparison to group 1 and placebo group (P&lt;0.01), as shown in figure (1).There was a significant decrease in e PAP in each group of studied groups after treatment (P&lt;0.01). As mean basal ePAP1 measures were (48 ±9, 43.5 ±16, 48.5 ±12) mmHg in group 1,2,3 respectively (P&gt;0.05).There were no significant differences between the studied groups regarding means of ePAP2 post-treatment were ( 42 ±9, 39 ±15, 44.5±8) mmHg in group 1,2,3 respectively (P&gt;0.05). However, the degree of severity of PH was more improved after treatment duration with sildenafil as in group 1 there were 5 patients downgraded from moderate to mild and 2 patients downgraded from severe to moderate after treatment. In group 2 there were 4 patients downgraded from moderate to mild PH and 2 patients downgraded from severe to moderate PH. In 3rd group (placebo group) only one patient downgraded from moderate to mild PH. There were 4 patients dropouts from the study two of them from group 2 (receiving 50mg) due to sildenafil related side effects appeared through the study. Conclusion This a clinical trial confirmed the efficiency of both 50mg and 25mg sildenafil daily dose in reducing e PAP and improving functional exercise capacity in chronic haemodialysis patients with pulmonary hypertension disease.

P2535Pregnant patients with pulmonary hypertension-the case of a medical centre

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Irtyuga ◽  
J Sefieva ◽  
E Karelkina ◽  
A Gabrelyan ◽  
A Bautin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Combination Therapy ◽  
Pulmonary Artery ◽  
Pregnant Women ◽  
Early Stage ◽  
Systolic Pressure ◽  
Systolic Pulmonary Artery Pressure ◽  
Group 1

Abstract Background Nowadays, Pulmonary Hypertension (PH) is one of the most pressing issues in cardiovascular disease. Subsequently, pregnant women have a high degree of risk of morbidity and mortality and this poses a big challenge. Studies show that very often PH occurs due to congenital heart disease and for this reason, it is recommended to avoid pregnancy or to terminate the pregnancy at an early stage. Women who choose to remain pregnant should be treated at specialized PH centers with the experience of managing PH during and after pregnancy. Purpose The main purpose of this study was to estimate the survival of pregnant pts with PH depending on the severity of PH and etiology. Methods 8336 women during delivery on admission were screened from the period spanning January 2014 to December 2016. Of this number, 4268 (51%) the medical records of pregnant women with cardiovascular disease were retrospectively reviewed to identify patients with coexisting PH and pregnancies. Data on 98 (1.18%) pts with PH were identified and included in the study. All patients' PH severity was measured by Doppler echocardiography. Pulmonary artery systolic pressure value of 35 to 50 mm Hg, 51 to 70 mm Hg, or greater than 71 mm Hg measured by echocardiography corresponded to the mild, moderate, or severe PH, respectively. Demographics, characteristics of PH and pregnancy, management and outcomes were as well analyzed. Results 54 cases (55%) were classified into WHO group 1, 40 cases (41%) in group 2 (reason –left heart disease), 4 cases (4%) in group 4 (reason - pulmonary thromboembolism), and none in group 3 or 5. The systolic pulmonary artery pressure was <50 mmHg in 70,4% of patients, 51–70 mmHg in 18,4% and ≥70 mmHg in 11,2% The median age was 28 years. All deaths occurred in women with PH in WHO group 1, with moderate or severe PH severity, and with NYHA grade of III to IV. Pulmonary vascular-targeted medications were used in all pts with severe PH and in some cases with moderate PH 14 pts (14%), but none was administered to pts with mild PH. During pregnancy, 9 pts took monotherapy of the sildenafil but 1 pregnant patient took a combination of therapy with iloprost. After delivery, 14 pts took monotherapy and 9 took combination therapy. This notwithstanding, 3 pts who took the combination therapy (3%), died within 15 days after delivery (9,14,15 days, respectively). All of them died from uncontrolled PH and heart failure after delivery. Conclusion Our study shows that maternal mortality is associated with the severity of PH. Mortality in pregnant patients with pulmonary hypertension is still the most discussed problem in cardiology and obstetrics. It is necessary to diagnose this disease at an early stage, prevent pregnancy in pts with severe to moderate PH as much as possible, continue observation, adequately apply therapy in order to help curtail this problem.

scholarly journals The Circulating MicroRNA-206 Level Predicts the Severity of Pulmonary Hypertension in Patients with Left Heart Diseases

2017 ◽  
Vol 41 (6) ◽  
pp. 2150-2160 ◽  
Author(s):  
Peng Jin ◽  
Wenzhu Gu ◽  
Yayu Lai ◽  
Wei Zheng ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Heart Diseases ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Pulmonary Artery Systolic Pressure ◽  
Circulating Microrna ◽  
Left Heart ◽  
Ventricular Ejection Fraction

Background: MicroRNA-206 (miR-206), a muscle-specific miRNA, regulates the growth of cardiac myocytes and pulmonary artery smooth muscle cells. However, it remains unknown whether miR-206 is involved in pulmonary hypertension (PH) due to left heart diseases (PH-LHD). This study was designed to investigate the correlation between miR-206 and PH in patients with LHD. Methods: In 82 consecutively enrolled LHD patients, we examined the serum levels of miR-206 and analyzed its correlations with pulmonary artery systolic pressure (PASP) and cardiac function. Another 36 age- and sex-matched subjects served as healthy controls. Results: The patients were divided into the LHD group (n=47, PASP<50 mmHg) and the PH-LHD group (n=35, PASP≥50 mmHg). The level of miR-206 was significantly decreased in the PH-LHD group compared with that of the LHD and healthy control groups. In addition, the miR-206 level was correlated with PASP (r=-0.305, p<0.001) but not with systemic blood pressure. Univariate analyses showed that miR-206, brain natriuretic peptide (BNP), left ventricular ejection fraction and left atrial longitudinal diameter (LAD) were significantly related to PASP. Multivariate regression analysis identified miR-206 as an independent predictive factor for PH. MiR-206 alone (cut-off <0.66) demonstrated a sensitivity of 68.60% and a specificity of 65.80% in predicting PH. Moreover, the combination of miR-206, BNP and LAD (cut-off 0.21) showed a sensitivity of 97.10% and a specificity of 80.30% in predicting PH in LHD patients. Conclusion: A decreased circulating miR-206 level was associated with increased PASP in LHD patients. Thus, the level of miR-206, especially combined with BNP and LAD, might be helpful in the detection of PH in LHD patients.

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.

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