VEGF synthesis is induced by prostacyclin and TGF-β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling

AbstractCOPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.

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Effects of the Neutral Endopeptidase Inhibitor, SCH 42495, on the Cardiovascular Remodelling Secondary to Chronic Hypoxia in Rats

Clinical Science ◽

10.1042/cs0870109 ◽

1994 ◽

Vol 87 (1) ◽

pp. 109-114 ◽

Cited By ~ 9

Author(s):

J. S. Thompson ◽

W. Sheedy ◽

A. H. Morice

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Chronic Hypoxia ◽

Neutral Endopeptidase ◽

Pulmonary Vasculature ◽

Vascular Remodelling ◽

Plasma Atrial Natriuretic Peptide ◽

And Control ◽

Pulmonary Vascular Remodelling ◽

Atrial Natriuretic

1. We have investigated the effects of inhibition of neutral endopeptidase on the cardiovascular remodelling secondary to chronic hypoxia in rats using a novel neutral endopeptidase inhibitor, SCH 42495. 2. Rats were divided into four groups, two of which were maintained in a normobaric, hypoxic chamber (10% O2) and two in room air. Animals received either neutral endopeptidase inhibitor, SCH 42495 (30 mg/kg), or aqueous methyl cellulose vehicle (0.4%) twice daily by oral gavage. 3. At 1, 3, 7, 10 and 14 days, animals (n = 4 per group for days 1, 3, 7 and 14, and n =8 for day 10) were killed. Hearts were dissected and weighed for determination of ventricular ratios, lungs were perfused with formol saline for histological examination of the pulmonary vasculature, and blood was collected for measurement of plasma atrial natriuretic peptide level. 4. Treatment with SCH 42495 caused a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy in hypoxic rats after 10 days. Plasma atrial natriuretic peptide levels were significantly elevated in both SCH 42495-treated and control hypoxic animals (n = 8) after 10 days when compared with the normoxic groups. However, there was no difference in plasma ANP levels between SCH 42495-treated and control chronic hypoxic groups at day 10. 5. Treatment with SCH 42495 leads to a decrease in cardiovascular remodelling secondary to chronic hypoxia in rats. A local action of atrial natriuretic peptide within the pulmonary vasculature may be responsible for this effect. Modulation of atrial natriuretic peptide may have therapeutic potential in the management of conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

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The Effects of a Neutral Stimulus (Buzzer) on Motor Responses and Disfluencies in Normal Speakers

Journal of Speech and Hearing Research ◽

10.1044/jshr.1201.179 ◽

1969 ◽

Vol 12 (1) ◽

pp. 179-184 ◽

Cited By ~ 7

Author(s):

Richard R. Martin ◽

Gerald M. Siegel

Keyword(s):

College Students ◽

Neutral Stimulus ◽

Motor Responses ◽

Control Subjects ◽

And Control ◽

Speaking Task

Seventy-two college students were divided into three groups: Button Push-Speech (BP-S), Speech-Button Push (S-BP), and Control. BP-S subjects pushed one of two buttons on signal for 8 min. During the last 4 min, depression of the criterion button caused a buzzer to sound. After the button-push task, subjects spoke spontaneously for 30 min. During the last 20 min, the buzzer was presented contingent upon each disfluency. S-BP subjects were run under the same procedures, but the order of button-push and speech tasks was reversed. Control subjects followed the same procedures as S-BP subjects, but no buzzer signal was presented at any time. Both S-BP and BP-S subjects emitted significantly fewer disfluencies during the last 20 min (Conditioning) than during the first 10 min (Baserate) of the speaking task. The frequency of disfluencies for Control subjects did not change significantly from Baserate to Conditioning. In none of the three groups did the frequency of pushes on the criterion button change significantly from minute to minute throughout the 8-min button-push session.

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P3257 Pulmonary vascular remodelling in pulmonary hypertension due to chronic heart failure

European Heart Journal ◽

10.1016/s0195-668x(03)95883-0 ◽

2003 ◽

Vol 24 (5) ◽

pp. 615

Author(s):

J DELGADO

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Chronic Heart Failure ◽

Vascular Remodelling ◽

Pulmonary Vascular Remodelling

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Circulating fibrocytes in pulmonary vascular remodelling

Pneumologie ◽

10.1055/s-0029-1202456 ◽

2009 ◽

Vol 63 (02) ◽

Author(s):

V Nikam ◽

G Hild ◽

R Schermuley ◽

R Dumitrascu ◽

N Weissmann ◽

...

Keyword(s):

Vascular Remodelling ◽

Pulmonary Vascular Remodelling ◽

Circulating Fibrocytes

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Tests for Platelet Changes, Acute Phase Reactants and Serum Lipids in Diabetes mellitus and Peripheral Vascular Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657283 ◽

1982 ◽

Vol 48 (03) ◽

pp. 289-293 ◽

Cited By ~ 17

Author(s):

B A van Oost ◽

B F E Veldhuyzen ◽

H C van Houwelingen ◽

A P M Timmermans ◽

J J Sixma

Keyword(s):

Diabetes Mellitus ◽

Vascular Disease ◽

Peripheral Vascular Disease ◽

Acute Phase ◽

Serum Lipids ◽

Diabetic Patients ◽

Peripheral Vascular ◽

Acute Phase Reactants ◽

Control Subjects ◽

And Control

SummaryPlatelets tests, acute phase reactants and serum lipids were measured in patients with diabetes mellitus and patients with peripheral vascular disease. Patients frequently had abnormal platelet tests and significantly increased acute phase reactants and serum lipids, compared to young healthy control subjects. These differences were compared with multidiscriminant analysis. Patients could be separated in part from the control subjects with variables derived from the measurement of acute phase proteins and serum lipids. Platelet test results improved the separation between diabetics and control subjects, but not between patients with peripheral vascular disease and control subjects. Diabetic patients with severe retinopathy frequently had evidence of platelet activation. They also had increased acute phase reactants and serum lipids compared to diabetics with absent or nonproliferative retinopathy. In patients with peripheral vascular disease, only the fibrinogen concentration was related to the degree of vessel damage by arteriography.

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ROLE OF PHARMACIST INTERVENTION ON COPD PATIENTS OF SELECTED AREAS IN CHITRADURGA: A KAP STUDY

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v8i2.586 ◽

2019 ◽

Vol 8 (2) ◽

Author(s):

Melvin K Mathews ◽

Abubaker Siddiq ◽

Bharathi D R

Keyword(s):

Illness Perceptions ◽

Pharmacist Intervention ◽

Cross Sectional Study ◽

Chronic Obstructive ◽

Cross Sectional ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Post Test ◽

Knowledge Practice ◽

And Control

Background: Chronic obstructive pulmonary disease (COPD) is preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Severity of the symptoms is increased during exacerbations. Objectives: The purpose of the study is to assess and improve the knowledge regarding COPD among study subjects. Materials and Methods: A Cross-sectional interventional study was carried out among the peoples in selected areas of the Chitradurga city for a period of six months. Result: A total 207 subjects enrolled in the study in that 155 male and 52 females. In our study mean score of post test was more (5.87±1.68) when compare to pre-test (2.63±1.46) which show significant increase in their knowledge after educating them (p=0.000). A total of 207 subjects were enrolled into the study. SPSS Software was used to calculate the statistical estimation. Paired t-test was used to detect the association status of different variables. Conclusion: The relatively good level of COPD awareness needs to be maintained to facilitate future prevention and control of the disease. This study had identified that negative illness perceptions should be targeted, so that they will not avoid patients from seeking for COPD treatment and adhere to it. Key words: Cross sectional study, Knowledge, practice, COPD.

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