scholarly journals Inhibition of BET Proteins Reduces Right Ventricle Hypertrophy and Pulmonary Hypertension Resulting from Combined Hypoxia and Pulmonary Inflammation

2018 ◽  
Vol 19 (8) ◽  
pp. 2224 ◽  
Author(s):  
Clovis Chabert ◽  
Saadi Khochbin ◽  
Sophie Rousseaux ◽  
Sylvie Veyrenc ◽  
Rebecca Furze ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Chronic Hypoxia ◽  
Pulmonary Inflammation ◽  
Male Rats ◽  
Hemodynamic Parameters ◽  
Terminal Domain ◽  
Co Morbidity ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Pulmonary hypertension is a co-morbidity, which strongly participates in morbi-mortality in patients with chronic obstructive pulmonary disease (COPD). Recent findings showed that bromodomain-containing proteins, in charge of reading histone acetylation, could be involved in pulmonary arterial hypertension. Our aim was to study the effect of I-BET151, an inhibitor of bromodomain and extra-terminal domain (BET), on the right ventricle hypertrophy and pulmonary hypertension, induced by a combination of chronic hypoxia and pulmonary inflammation, as the two main stimuli encountered in COPD. Adult Wistar male rats, exposed to chronic hypoxia plus pulmonary inflammation (CHPI), showed a significant right ventricle hypertrophy (+57%, p < 0.001), an increase in systolic pressure (+46%, p < 0.001) and in contraction speed (+36%, p < 0.001), when compared to control animals. I-BET151 treated animals (CHPI-iB) showed restored hemodynamic parameters to levels similar to control animals, despite chronic hypoxia plus exposure to pulmonary inflammation. They displayed lower right ventricle hypertrophy and hematocrit compared to the CHPI group (respectively −16%, p < 0.001; and −9%, p < 0.05). Our descriptive study shows a valuable effect of the inhibition of bromodomain and extra-terminal domain proteins on hemodynamic parameters, despite the presence of chronic hypoxia and pulmonary inflammation. This suggests that such inhibition could be of potential interest for COPD patients with pulmonary hypertension. Further studies are needed to unravel the underlying mechanisms involved and the net benefits of inhibiting adaptations to chronic hypoxia.

Pulmonary hypertension is attenuated and ventilation-perfusion matching is maintained during chronic hypoxia in deer mice native to high altitude

2021 ◽  
Author(s):  
Claire M. West ◽  
Oliver H. Wearing ◽  
Rod G. Rhem ◽  
Graham R. Scott
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Right Ventricle ◽  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Deer Mice ◽  
Maladaptive Response ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Hypoxia at high altitude can constrain metabolism and performance, and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice (Peromyscus maniculatus) native to high altitude have attenuated this maladaptive response to chronic hypoxia, and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O2, simulating the O2 pressure at 4300 m) for 6-8 weeks. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg (P = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SDQ) from 0.55 to 0.86 (P = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.

scholarly journals Cyclosporin A Inhibits Hypoxia-induced Pulmonary Hypertension and Right Ventricle Hypertrophy

2006 ◽  
Vol 174 (6) ◽  
pp. 699-705 ◽  
Author(s):  
Nathalie Koulmann ◽  
Valérie Novel-Chaté ◽  
André Peinnequin ◽  
Rachel Chapot ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Cyclosporin A ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

scholarly journals Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

2020 ◽  
Vol 21 (19) ◽  
pp. 7077
Author(s):  
Olga Sadowska ◽  
Marta Baranowska-Kuczko ◽  
Anna Gromotowicz-Popławska ◽  
Michał Biernacki ◽  
Aleksandra Kicman ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Plasminogen Activator ◽  
Leukocyte Count ◽  
Plasma Concentrations ◽  
Lung Edema ◽  
Human Pulmonary Artery ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats. PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation. CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH. Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.

Supplementation of Creatine and Ribose Prevents Apoptosis and Right Ventricle Hypertrophy in Hypoxic Hearts

2013 ◽  
Vol 19 (39) ◽  
pp. 6873-6879 ◽  
Author(s):  
Anna Caretti ◽  
Paola Bianciardi ◽  
Marina Marini ◽  
Provvidenza Abruzzo ◽  
Alessandra Bolotta ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

scholarly journals TETRALOGI FALLOT DAN ATRESIA PULMONAL

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Alice I. Supit ◽  
Erling D. Kaunang
Keyword(s):  
Patent Ductus Arteriosus ◽  
Right Ventricle ◽  
Tetralogy Of Fallot ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Ductus Arteriosus ◽  
Ventricle Hypertrophy ◽  
The Right ◽  
Right Ventricle Hypertrophy ◽  
Patent Ductus

Abstract: Congenital heart disease is a structural defect due to the malformation of the heart, aorta, and or great blood vessels. It is the most frequent congenital malformation in newborn babies. Tetralogy of Fallot is one of the congenital heart diseases (CHD) with central cyanosis, and covers 5-10% of all CHD. We reported a boy of one year old with Tetralogy of Fallot and pulmonal atresia (ToF-PA), associated with bronchopneumonia. The diagnosis was based on anamnesis, physical examination, and other supporting examinations. The chest X-ray showed a normal sized heart (CTR 57%) with coer-en-sabot shape, and right and left parahilar infiltration, which resulted in bronchopneumonia and ToF. The electrocardiography showed a right deviation of axis and a hypertrophy of the right ventricle; the echocardiography showed a right ventricle hypertrophy, an over-riding aorta, a large malalignment of the ventricular septal defect, no visualization of pulmonar artery, and no visualization of patent ductus arteriosus (PDA). Conclusion: Based on all the tests performed, the diagnosis of this patient was Tetralogy of Fallot and pulmonal atresia (ToF-PA), associated with bronchopneumonia. The prognosis related to bronchopneumonia in this case was good due to the use of antibiotics. Keywords: tetralogy of Fallot, pulmona atresia, bronchopneumonia.  Abstrak: Penyakit jantung bawaan (PJB) ialah kelainan struktural akibat malformasi jantung, aorta dan atau pembuluh darah besar, dan merupakan kelainan kongenital tersering pada bayi baru lahir. Tetralogi Fallot merupakan salah satu PJB dengan sianosis sentral, dan mencakup 5-10% dari seluruh PJB. Kami melaporkan kasus seorang anak laki-laki berusia satu tahun dengan Tetralogi Fallot dan atresia pulmonal (ToF-PA) disertai bronkopneumonia. Diagnosis ditegakkan melalui anamnesis, pemeriksaan fisik, dan pemeriksaan penunjang. Hasil ekspertisi foto toraks AP memperlihatkan ukuran jantung normal (CTR 57%) berbentuk coer-en-sabot, dan pada paru-paru terlihat infiltrat parahilar kanan dan kiri serta corakan vaskular paru berkurang yang menunjukkan suspek bronkopneumonia dan ToF. Elektrokardiografi memperlihatkan deviasi aksis ke kanan dan hipertrofi ventrikel kanan, dan pada ekokardiografi tampak right ventricle hypertrophy, overriding aorta, VSD malalignment besar, tidak tampak visualisasi arteri pulmonal, dan tidak tampak patent ductus arteriosus (PDA) dengan hasil Tetralogi Fallot dan atresia pulmonal. Simpulan: Berdasarkan hasil pemeriksaan yang dilakukan, diagnosis pasien ini ialah Tetralogi Fallot dan atresia pulmonal (ToF-PA) disertai bronkopneumonia. Prognosis bronkopenumonia pada kasus ini baik yang dapat diatasi dengan antibiotika.Kata kunci: tetralogi Fallot, atresia pulmonal, bronkopneumonia.  

scholarly journals Resistance training prevents right ventricle hypertrophy in rats exposed to secondhand cigarette smoke

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0236988
Author(s):  
Ana Caroline Rippi Moreno ◽  
Gisele Alborghetti Nai ◽  
Caroline Pancera Laurindo ◽  
Karen Cristina Rego Gregorio ◽  
Tiago Olean-Oliveira ◽  
...  
Keyword(s):  
Resistance Training ◽  
Right Ventricle ◽  
Cigarette Smoke ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

scholarly journals MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

2013 ◽  
Vol 304 (2) ◽  
pp. H269-H281 ◽  
Author(s):  
R. Dale Brown ◽  
S. Kelly Ambler ◽  
Min Li ◽  
Timothy M. Sullivan ◽  
Lauren N. Henry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Cardiac Myocyte ◽  
Chronic Hypoxia ◽  
Regulatory Protein ◽  
Right Heart Failure ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
The Right

Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2−/− mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O2, 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2−/− mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2−/− mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH.

scholarly journals Ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate Prevents Progression of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

2017 ◽  
Vol 3 (1) ◽  
pp. 31
Author(s):  
S. M. Malik ◽  
Satyanarayan Deep ◽  
Rahul Ranjan ◽  
A. K. Prasad ◽  
Dipti N Prasad ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Pulmonary Vasculature ◽  
Treatment Groups ◽  
Future Drug ◽  
Wet Weight ◽  
Pulmonary Arterial ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

<p>Therapies to prevent onset and progression of pulmonary arterial pressure are not very effective yet. This study was designed to investigate the effects of a novel dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) on pathogenesis of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). For the same purpose, rats were injected intraperitoneally (i.p.) a single dose (60 mg/kg) of MCT which led to development of PAH in 21 days. MCT insult caused high mortality, pulmonary vascular and parenchymal remodelling. Since the course of PAH pathogenesis is characterised by an early onset and progression phases, H-DHPM was administered i.p. at 30 mg/kg dosage in MCT pre-injected animals either from day 0 through day 21 or day 14 though day 21 of MCT injection in two separate treatment groups. H-DHPM significantly improved survival, prevented remodelling of pulmonary vasculature and parenchyma and subsequently ameliorated PAH pathogenesis. Moreover, we observed significant decrease in right ventricle hypertrophy, measured by wet weight of right ventricle (RV) divided by wet weight of left ventricle plus septum (LV+S), in H-DHPM treated groups as compared to MCT injected animals. These findings suggest H-DHPM not only prevented development of PAH but also treated the PAH pathogenesis in progressive phase. In conclusion, our data determines H-DHPM, might be a future drug for the prevention of PAH.</p>

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