scholarly journals MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

2016 ◽  
Vol 311 (3) ◽  
pp. H689-H698 ◽  
Author(s):  
Sachindra Raj Joshi ◽  
Vidhi Dhagia ◽  
Salina Gairhe ◽  
John G. Edwards ◽  
Ivan F. McMurtry ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Right Heart ◽  
Biochemical Processes ◽  
Pulmonary Arterial ◽  
Direct Target ◽  
The Right ◽  
Mitofusin 1

Heart failure, a major cause of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), is an outcome of complex biochemical processes. In this study, we determined changes in microRNAs (miRs) in the right and left ventricles of normal and PAH rats. Using an unbiased quantitative miR microarray analysis, we found 1) miR-21-5p, miR-31-5 and 3p, miR-140-5 and 3p, miR-208b-3p, miR-221-3p, miR-222-3p, miR-702-3p, and miR-1298 were upregulated (>2-fold; P < 0.05) in the right ventricle (RV) of PAH compared with normal rats; 2) miR-31-5 and 3p, and miR-208b-3p were upregulated (>2-fold; P < 0.05) in the left ventricle plus septum (LV+S) of PAH compared with normal rats; 3) miR-187-5p, miR-208a-3p, and miR-877 were downregulated (>2-fold; P < 0.05) in the RV of PAH compared with normal rats; and 4) no miRs were up- or downregulated with >2-fold in LV+S compared with RV of PAH and normal. Upregulation of miR-140 and miR-31 in the hypertrophic RV was further confirmed by quantitative PCR. Interestingly, compared with control rats, expression of mitofusin-1 (MFN1), a mitochondrial fusion protein that regulates apoptosis, and which is a direct target of miR-140, was reduced in the RV relative to LV+S of PAH rats. We found a correlation between increased miR-140 and decreased MFN1 expression in the hypertrophic RV. Our results also demonstrated that upregulation of miR-140 and downregulation of MFN1 correlated with increased RV systolic pressure and hypertrophy. These results suggest that miR-140 and MFN1 play a role in the pathogenesis of PAH-associated RV dysfunction. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/mir140-and-right-heart-hypertrophy/ .

scholarly journals The right ventricle in pulmonary arterial hypertension

2014 ◽  
Vol 23 (134) ◽  
pp. 476-487 ◽  
Author(s):  
Robert Naeije ◽  
Alessandra Manes
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Systolic Function ◽  
Fluid Management ◽  
Right Heart ◽  
Heart Chamber ◽  
Right Heart Catheterisation ◽  
Pulmonary Arterial ◽  
The Right

Pulmonary arterial hypertension (PAH) is a right heart failure syndrome. In early-stage PAH, the right ventricle tends to remain adapted to afterload with increased contractility and little or no increase in right heart chamber dimensions. However, less than optimal right ventricular (RV)–arterial coupling may already cause a decreased aerobic exercise capacity by limiting maximum cardiac output. In more advanced stages, RV systolic function cannot remain matched to afterload and dilatation of the right heart chamber progressively develops. In addition, diastolic dysfunction occurs due to myocardial fibrosis and sarcomeric stiffening. All these changes lead to limitation of RV flow output, increased right-sided filling pressures and under-filling of the left ventricle, with eventual decrease in systemic blood pressure and altered systolic ventricular interaction. These pathophysiological changes account for exertional dyspnoea and systemic venous congestion typical of PAH. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterisation measurements. Treatment of RV failure in PAH relies on: decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimise ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. To date, there has been no report of the efficacy of drug treatments that specifically target the right ventricle.

scholarly journals RETROSPECTIVE EFFICACY ANALYSIS OF ACUTE VASOREACTIVE TEST AS A CRITERIA FOR SURGERY IN CHILDREN WITH INBORN LEFT-TO-RIGHT BLOOD SHUNTING AND PULMONARY ARTERIAL HYPERTENSION

2018 ◽  
pp. 41-46
Author(s):  
A. Mullen ◽  
G. Butrous ◽  
K. Abzaliev
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Retrospective Analysis ◽  
Vascular Resistance ◽  
Systolic Pressure ◽  
Pulmonary Arterial ◽  
Group 2 ◽  
The Right ◽  
Group 1

Aim. Retrospective analysis of efficacy of the acute vasoreactive test (AVRT) as a criteria for operability of children with inborn left-to-right blood shunting complicated by pulmonary arterial hypertension (IRLBS-PAH), by an experience of one center.Material and methods. Retrospective analysis of the data of right heart chambers catheterization and echocardiographic study from 29 case histories of BS-PAH patients during 2012-2016. Results of AVRT are interpreted by modified Barst criteria (decline of pulmonary vascular resistance index, PVRI, and relation of PVRI to the index of systemic vascular resistance, SVR more than 20%, and the and PVRI <6 Wood units/m2 in PVR/SVR <0,3). In accordance with the results of AVRT, patients were selected to two main groups: group 1 — children with positive response, group 2 — children with negative response. After correction of the inborn defect in bith groups, following assessment of cardiovascular system condition was done by echocardiographical study in one week and one month. Metrics of echocardiography data was indexed. For the defect of interventricular septum (DIVS), indexation of the size was done via the relation to aortic root diameter, that was measured in parasternal position, longitudinal axis. Systolic pressure in the right ventricle was measured by the velocity of tricuspid regurgitation, measured in apical four-chamber position. Mean values with the standard deviation and p-values were calculated in R studio 2017 software, v.1.0.153.Results. Among 29 patients, girls to boys relation was 4,8:1. Mean age 6,0±4,9 y. o. For group 1: median of DIVS 1,4 with the value of additional shunting 9,93±9,39 mm, baseline systolic pressure in the right ventricle (SPRV) 57,96±20,16 mmHg, in one month after surgery 38,96±14,16 mmHg. No complications registered. In the second group, median DIVS 0,4 with additional shunting 3,3±0 mm. Baseline SPRV 66,05±17,27 mmHg, with the decline in one month after transcatheter closure to 57,4±17,35 mmHg. During the early post-surgery period, in 2 patients of group 2 there was pulmonary crisis, treated with inhalatory iloprost. Conclusion. Acute vasoreactive test is effective criteria of operability assessment of inborn left-to-right blood shunting, complicated by pulmonary arterial hypertension, in pediatrics.

scholarly journals Potts Shunt in Children With Familial Primary Pulmonary Hypertension: A Case Report and Brief Literature Review

2021 ◽  
Vol 9 (3) ◽  
pp. 247-254
Author(s):  
Mahya Mobinikhaledi ◽  
◽  
Ali Arjmand Shabestari ◽  
Yazdan Ghandi ◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Medical Treatment ◽  
Right Heart Failure ◽  
Right Heart ◽  
Pulmonary Arterial ◽  
The Right

Introduction: The primary concern about Familial Pulmonary Arterial Hypertension (FPAH) is the development of right heart failure, which ultimately leads to sudden death. Despite recent advances in pharmacological therapy, the mortality rate in children is still high, emphasizing the importance of novel treatments. Moreover, there is still no definitive treatment for children with severe pulmonary hypertension. The consequences of right heart failure led to the proposal of a surgical approach, the Potts shunt, to decompress the right ventricle, providing shunting of deoxygenated blood to lower extremities and improving overall cardiac output. This surgical technique creates an anastomosis between the left pulmonary artery and the descending aorta, providing a palliative treatment to off-load the right ventricle. Case Presentation: We report an 11-year-old girl with familial pulmonary arterial hypertension and right ventricular failure who benefited from a Potts shunt with good mid-term results. The patient was diagnosed at the age of 5 when she had a history of fainting and persistent syncope. The patient was under medical treatment therapy with bosentan, sildenafil, acetylsalicylic acid, and warfarin for six years. The results of molecular genetic testing, which was confirmed with direct sequencing of the Bone Morphogenetic Protein Receptor Type 2 (BMPR2) gene, revealed a heterozygous pathogenic mutation. Since she was diagnosed with Pulmonary Arterial Hypertension (PAH), she lost her grandmother, an aunt, and father because of PAH. Her 14-year-old sister also had mutated the BMPR2 gene without developing FPAH. Conclusions: The Potts shunt provides an interventional step for palliation of patients with familial pulmonary hypertension and severe right heart failure refractory to medical treatment. It opens the door to the possibility of lung transplantation in the future. We did not see any complications within 6 years after placing the Potts shunt.

scholarly journals Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline

2018 ◽  
Vol 96 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Rafaela Siqueira ◽  
Rafael Colombo ◽  
Adriana Conzatti ◽  
Alexandre Luz de Castro ◽  
Cristina Campos Carraro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Protein Expression ◽  
Arterial Hypertension ◽  
Female Rats ◽  
Antioxidant Defenses ◽  
Thioredoxin 1 ◽  
Pulmonary Arterial ◽  
The Right

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg−1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor β (ER-β). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.

scholarly journals The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle

2015 ◽  
Vol 46 (3) ◽  
pp. 832-842 ◽  
Author(s):  
Emmy Manders ◽  
Silvia Rain ◽  
Harm-Jan Bogaard ◽  
M. Louis Handoko ◽  
Ger J.M. Stienen ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Exercise Intolerance ◽  
Muscle Dysfunction ◽  
Striated Muscles ◽  
Pulmonary Arterial ◽  
The Right ◽  
The Impact

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.

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