scholarly journals Preventive training does not interfere with mRNA-encoding myosin and collagen expression during pulmonary arterial hypertension

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0244768
Author(s):  
Thaoan Bruno Mariano ◽  
Anthony César de Souza Castilho ◽  
Ana Karenina Dias de Almeida Sabela ◽  
André Casanova de Oliveira ◽  
Sarah Santiloni Cury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Functional Capacity ◽  
Adaptation Period ◽  
Cross Sectional ◽  
Collagen Expression ◽  
Pulmonary Arterial ◽  
The Impact

To gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S, n = 8); Control with Training (T, n = 8); Sedentary with Pulmonary Arterial Hypertension (SPAH, n = 8); and Pulmonary Arterial Hypertension with Training (TPAH, n = 8). All rats underwent a two-week adaptation period; T and TPAH group rats then proceeded to an eight-week training period on a treadmill. At the beginning of the 11th week, S and T groups received an intraperitoneal injection of saline, and SPAH and TPAH groups received an injection of monocrotaline (60 mg/kg). Rats in the T and TPAH groups then continued with the training protocol until the 13th week. We assessed exercise capacity, echocardiography analysis, Fulton’s index, cross-sectional areas of cardiomyocytes, collagen content and types, and fractal dimension (FD). Transcript abundance of myosins and extracellular matrix genes were estimated through reverse transcription-quantitative PCR (RT-qPCR). When compared to the SPAH group, the TPAH group showed increases in functional capacity and pulmonary artery acceleration time/pulmonary ejection time ratio and decreases in Fulton’s index and cross-sectional areas of myocyte cells. However, preventive exercise did not induce alterations in col1a1 and myh7 gene expression. Our findings demonstrate that preventive exercise improved functional capacity, reduced cardiac hypertrophy, and attenuated PH development without interfering in mRNA-encoding myosin and collagen expression during PAH.

scholarly journals Preventive training interferes with mRNA-encoding myosin 7 and collagen I expression during pulmonary arterial hypertension

2020 ◽  
Author(s):  
Thaoan Bruno Mariano ◽  
Anthony César de Souza Castilho ◽  
Ana Karenina Dias de Almeida Sabela ◽  
André Casanova de Oliveira ◽  
Sarah Santiloni Cury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Cardiac Dysfunction ◽  
Positive Impact ◽  
Control Group ◽  
Pulmonary Arterial ◽  
The Impact

AbstractTo gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S; n=8); Control with Training (T; n=8); Sedentary with Pulmonary Arterial Hypertension (SPAH; n=8); and Pulmonary Arterial Hypertension with Training (TPAH; n=8). The rats trained for thirteen weeks on a treadmill. They had two weeks of adaptation training. The PAH was induced by application of monocrotaline 60 mg/kg. Consequential right ventricular dysfunction was observed after the 10th week of training. Rats in the control group received saline application. At the end of the 13th week, echocardiography analysis confirmed cardiac dysfunction. Collagen content and organization was assessed through picrosirius red staining and fractal dimension (FD) analysis, respectively. Transcript abundance was estimated through reverse transcription-quantitative PCR (RT-qPCR). Cardiac dysfunction was confirmed by the reduction in maximum pulmonary artery velocity and pulmonary artery acceleration time. Through histomorphometric assessment, we found no differences in the interstitial collagen FD between groups. Regarding gene expression, myh7 gene expression was upregulated in the TPAH group. However, this did not occur with the S group. PAH also increased the mRNA abundance of col1a1 in the SPAH and TPAH groups. Moreover, the TPAH group showed a higher abundance of this gene when compared to the S group. With these findings, we concluded that preventive exercise had a positive impact on compensated hypertrophy during pulmonary hypertension. This can be explained in part by the modulation of the extracellular matrix and myosin gene expression in trained rats.

scholarly journals EXPRESS: Association of daily physical activity with psychosocial aspects and functional capacity in patients with Pulmonary Arterial Hypertension: a cross-sectional study

2021 ◽  
pp. 204589402199995
Author(s):  
Layse Nakazato Lima ◽  
Felipe Mendes ◽  
Ilma Paschoal ◽  
Daniela Oliveira ◽  
Marcos Mello Moreira ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Functional Capacity ◽  
Daily Physical Activity ◽  
Cross Sectional ◽  
Pulmonary Arterial ◽  
The Mean

Pulmonary arterial hypertension (PAH) impairs exercise tolerance and daily physical activity (PA). Aside from the hemodynamic limitations, physical, cognitive and emotional factors may play a relevant and as yet unexplored role. We investigated whether there is an association between the PA level and psychological disorders, health-related quality of life, and daily activities. We also searched for an association of the PA level with clinical factors and functional capacity. This was an analytical, cross-sectional, observational study conducted in a Brazilian University Hospital. Twenty stable PAH subjects wore an accelerometer for a week and completed an activity diary. They answered the quality of life questionnaire (SF-36), as well as the anxiety and depression scale (HADS), and the Manchester Respiratory Activities of Daily Living questionnaire (MRADL). Transthoracic echocardiography, the 6-Minute walk test (6MWT), the 1-minute sit-to-stand test (STST), and spirometry were performed. For statistical analysis we used Chi-square tests or Fisher's test as appropriate and the Mann-Whitney test to compare numerical values between two groups. The relationship between the parameters was assessed using the Spearman correlation test. The mean age was 44.3 years, 80% were women, 80% had idiopathic PAH, and 20% had connective tissue disease . The mean daily step count was 4,280 ± 2,351, and the mean activity time was 41.6 ± 19.3 minutes. The distance covered (6MWT) was 451.5 m, and the number of movements (1-STST) was 23.8. Thirty percent scored positive for anxiety, and 15% for depression (HADS). There was a significant correlation between accelerometer data and walking distance (6MWT), number of movements (1-STST), level of daily physical activity (MRADL), and depression symptoms. Our findings support the hypothesis that other aspects beyond physical and hemodynamic ones might impact the daily physical activity of patients with PAH.

scholarly journals Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 779
Author(s):  
Daria S. Kostyunina ◽  
Paul McLoughlin
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Sex Chromosomes ◽  
Bone Morphogenetic Protein 2 ◽  
Sex Dimorphism ◽  
Pulmonary Arterial ◽  
The Impact

Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.

scholarly journals Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with chronic thromboembolic pulmonary hypertension (CTEPH): a qualitative interview study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Brooke Currie ◽  
Evan Davies ◽  
Amélie Beaudet ◽  
Larissa Stassek ◽  
Leah Kleinman
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Shortness Of Breath ◽  
Response Options ◽  
Qualitative Interview Study ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
The Impact

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients’ lives is needed to optimally assess the impact of the disease and treatment. Objectives This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients’ lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. Methods Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™‘s instructions, items, and response options. Results Participants (N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an “extremely important” symptom, and seven participants rated fatigue as “extremely important.” The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. Conclusions The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.

Reliability and responsiveness of incremental shuttle walk test to estimate exercise capacity in patients with pulmonary arterial hypertension

2020 ◽  
Vol 16 (3) ◽  
pp. 179-185
Author(s):  
R. Ishrat ◽  
A. Mujaddadi ◽  
M.S. Ali ◽  
D. Talwar ◽  
M.E. Hussain
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Exercise Capacity ◽  
Intraclass Correlation ◽  
World Health ◽  
Minimal Detectable Change ◽  
Walk Test ◽  
Cross Sectional ◽  
Suitable Alternative ◽  
Pulmonary Arterial

The purpose of the present study was to evaluate the reliability and responsiveness of the incremental shuttle walk test (ISWT) to estimate exercise capacity in patients with pulmonary arterial hypertension (PAH). This was a cross-sectional longitudinal study performed on stable PAH patients (n=30, mean age ± standard deviation, 60±13.6 years) with World Health Organization functional class II & III. Reliability was assessed by comparing the distance covered between ISWT-1 (initial) and ISWT-2 (retest). Responsiveness was determined by comparing the distance covered in the ISWT-3 post pulmonary rehabilitation (PR) to the ISWT-1. The distance covered between ISWT-1 (177±87.85 m) and ISWT-2 (191.67±96.39 m) was not statistically significant. The result of the relative reliability has shown to be excellent with an intraclass correlation coefficient (ICC2,1 = 0.98, 95%CI = 0.95-0.99). Absolute reliability was evaluated through the standard error of the measurement and minimal detectable change at a 95% confidence interval (MDC95) were 12.29 and 33.9 m, respectively. Bland Altman plot showed good agreement between the two ISWTs. Following PR, the effect size (ES=0.78) and standardised response mean (SRM=1.50) were moderate and large respectively. ISWT is considered to be a reliable and responsive measure to estimate exercise capacity in patients with PAH. The ISWT may be considered a suitable alternative tool over a 6-min walk test and in the absence of equipment availability or expertise for conducting cardiopulmonary exercise test for the assessment of exercise capacity in these patients.

scholarly journals Patients with systemic sclerosis-associated pulmonary arterial hypertension express a genomic signature distinct from patients with interstitial lung disease

2018 ◽  
Vol 3 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Matthew Moll ◽  
Romy B Christmann ◽  
Yuqing Zhang ◽  
Michael L Whitfield ◽  
Yu Mei Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Interstitial Lung Disease ◽  
Arterial Hypertension ◽  
Lung Disease ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Gene Expression Profiles ◽  
Pulmonary Arterial

Objective: Pulmonary arterial hypertension and interstitial lung disease are major causes of mortality in systemic sclerosis. We used a previously identified microarray biomarker to determine whether systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease patients demonstrate distinct gene expression profiles. Methods: Peripheral blood mononuclear cells were collected from healthy controls ( n = 10), systemic sclerosis patients without pulmonary hypertension (systemic sclerosis-no pulmonary arterial hypertension, n = 39), and systemic sclerosis-pulmonary arterial hypertension patients ( n = 21; mean pulmonary arterial pressure ≥25, pulmonary capillary wedge pressure ≤15, and pulmonary vascular resistance ≥3 Wood units) diagnosed by right heart catheterization. Systemic sclerosis-interstitial lung disease patients were defined as those with evidence of fibrosis on chest computed tomography and significant restriction (forced vital capacity <70% predicted, n = 11). Systemic sclerosis-pulmonary arterial hypertension biomarker included 69 genes selected by unbiased statistical screening of three publicly available microarray studies. RNA levels were measured by NanoString Technologies. Gene expression levels that were significantly correlated with pulmonary arterial hypertension (multiple statistical measures) were chosen as inputs into a forward selection logistic regression model. Results: When interstitial lung disease patients were included ( n = 64), four genes (S100P, CD8B1, CCL2, and TIMP1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.83). Without interstitial lung disease patients ( n = 53), two genes (THBS1 and CD8B1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.80). When examining systemic sclerosis patients with borderline elevated pulmonary pressures (mean pulmonary arterial pressure = 21–24 mmHg), gene expression changes closely resembled the systemic sclerosis-pulmonary arterial hypertension group, except for THBS1. Conclusion: Systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease have similar but distinct gene expression profiles. Many gene expression changes occur early in the disease course, potentially allowing early detection. THBS1 appears to be an important mediator in the development of pulmonary arterial hypertension-predominant phenotype. Further prospective investigation is warranted.

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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