Changes in elastic fibres in the small airways and alveoli in COPD

Black, Peter; Ching, Pst; Beaumont, Brent; Ranasinghe, Sachinka; Taylor, Glen; Merrilees, Mervyn J.

doi:10.1183/09031936.00017207

Cited by 136 publications

(118 citation statements)

References 25 publications

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“…We further show that the decrease in insoluble elastin induced by CSE can be blocked by a siRNA directed at V1, which in turn can be countered by exogenous CS, the component of V1 and other CS-rich matrix proteoglycans known to inhibit the deposition of insoluble elastin (Hinek et al, 2000;Huang et al, 2006;Black et al, 2008). …”

Section: Discussionmentioning

confidence: 73%

“…This process is inhibited in the presence of CS (Hinek et al, 2000). Elastin binding protein, an inactive variant of galactosidase, has a binding pocket for CS which, when occupied, releases tropoelastin prematurely and before transfer to the microfibrils (Hinek et al, 2000;Black et al, 2008). A consequence of this action is that potential repair of elastic fibers does not take place in the presence of elevated levels of pericellular versican or CS, even though cells in repair situations still have the capacity to synthesise tropoelastin.…”

Section: Exogenous Cs Prevents Insoluble Elastin Accumulationmentioning

confidence: 99%

“…Several studies have shown chondroitin sulfate (CS) rich matrix proteoglycans, such as versican, inhibit this process (Hinek et al, 1991;Hinek et al, 2000;Huang et al, 2006;Black et al, 2008), and COPD lungs may also have increased content of CS proteoglycans in alveolar walls (Deslee et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts

Xu¹,

Lu²,

Zhang³

et al. 2015

Respiratory Physiology & Neurobiology

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of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts, Respiratory Physiology and Neurobiology (2015), http://dx.doi.org/10.1016/j.resp.2015. 05.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HighlightsWe find extracellular matrix protein versican 1 is in creased by cigarette smoke extract solution in lung fibroblasts.Versican 1 knockdown restore cigarette-related elastin loss through chondroitin sulfate decrease.Exgenous chondroitin sulfate could block the beneficent effect brought by versican 1 knockdown. Page 2 of 21A c c e p t e d M a n u s c r i p t Abstract COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican 1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS, did not affect tropoelastin production, but blocked the CSE-induced loss in insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence of V1 siRNA. These findings confirm that V1 and CS impair the assembly of tropoelastin monomers into insoluble fibers, and further demonstrate that specific knockdown of V1 alleviates the impaired assembly of elastin seen in cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role for this protein in the pathophysiology of COPD.

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Section: Discussionmentioning

confidence: 73%

Section: Exogenous Cs Prevents Insoluble Elastin Accumulationmentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts

Xu¹,

Lu²,

Zhang³

et al. 2015

Respiratory Physiology & Neurobiology

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“…As a consequence, there may be increase in inspiratory airflow resistance followed by derangement of ventilatory variables. [31][32][33][34] It has also been suggested, the first component of PR program that is, regular pursed lip breathing has been suggested to decrease the amount of the trapped air in the lungs followed by decreased work of breathing 35 as well as relief of dyspnea. 35,36 Moreover, regular diaphragmatic breathing (another important component of our PR program) along with pursed lip breathing have also been proposed to be a cause of strengthening of the diaphragm and abdominal muscles followed by decrement in energy utilization for breathing.…”

Section: Discussionmentioning

confidence: 99%

Effects of Pulmonary Rehabilitation on Lung Functions in Patients with COPD

Ahmed¹,

Begum

Sultana

et al. 2014

J Bangladesh Soc Physiol

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Background: The importance of pulmonary rehabilitation (PR) as a therapeutic measure for COPD patients is well known. Objective: To evaluate the effects of PR program by pursed lip breathing (PLB) and diaphragmatic breathing (DB) on FVC, FEV 1 , FEV 1 /FVC ratio in male patients with moderate stable COPD. Methods: This prospective study was conducted in the Department of Physiology, BSMMU, Dhaka from July 2010 to June 2011 on 116 male stable moderate COPD patients aged 50 to 65 years. They were enrolled from the out patient department of the Department of Medicine of BSMMU and NIDCH Dhaka. They were grouped as control (56 patients without PR) and experimental (60 patients with PR). The experimental patients were advised to perform PR program for 30 minutes duration per session at home twice daily, for consecutive 60 days along with the standard drug treatment of COPD. On the contrary, the control patients were advised to continue their standard drug treatment alone for consecutive 60 days. For the assessment of spirometric lung function status, FVC, FEV 1 , FEV 1 /FVC ratio of all subjects were recorded on day 0 and day 60 for both the group by a portable digital MicroDL Spirometer and the statistical analysis was done by independent sample 't' test and paired Student's 't' test. Results: FVC and FEV 1 value were significantly increased in comparison to the control patients after 60 days of follow up. On the other hand, post exercise value of FEV 1 /FVC ratio was decreased but it was not statistically significant. Conclusion: The study reveals improvement of lung functions with this sort of combination of PR program in stable COPD patients.

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“…Estudos em humanos demonstraram o aumento de neutrófilos no pulmão de pacientes com DPOC e relataram o aumento de produtos da elastase na urina e no plasma desses pacientes 35 . Também foi publicado recentemente que o volume de fibras elásticas nos alvéolos e pequenas vias aéreas está reduzido nos pacientes com DPOC 36 . No entanto, Rufino et al demonstraram que a quantidade de fibras elásticas não está reduzida no parênquima pulmonar de pacientes com enfisema quando comparado a controles não tabagistas e sugeriram que as fibras pudessem estar rompidas ou funcionalmente alteradas 37 .…”

Section: Neutrófilosunclassified

Células inflamatórias e seus mediadores na patogênese da DPOC

Costa

Rufino

Silva

2009

Rev. Assoc. Med. Bras.

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Artigo de revisão ResumoA doença pulmonar obstrutiva crônica (DPOC) é causada por processo inflamatório crônico que limita o fluxo aéreo, sendo sua principal causa o tabagismo. Conforme dados da Organização Mundial de Saúde (OMS), a DPOC será a quarta causa de mortalidade em 2020, atrás apenas das doenças vasculares, cardíacas e cerebral, além das neoplasias. Apesar do enorme crescimento da prevalência e da mortalidade da DPOC, não existe nenhuma terapêutica que consiga controlar a evolução da doença estabelecida. O processo inflamatório crônico causado pelos gases da fumaça de tabaco desencadeia alterações estruturais que predominam nas pequenas vias aéreas (menores que 2 mm). Essa agressão provoca um processo inflamatório que conta com a participação não apenas de macrófagos, linfócitos e neutrófilos, mas células estruturais como epiteliais, musculares e fibroblastos. Atualmente, a interação entre macrófagos e linfócitos, especialmente CD8+, tem sido implicada na patogênese da DPOC. Quimiocinas como CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC e CCL5/RANTES têm sido descritas como possíveis responsáveis pelo recrutamento de linfócitos T e monócitos sanguíneos, facilitando o aumento de macrófagos alveolares e linfócitos T CD8+ no parênquima dos pacientes com DPOC. Conhecer melhor como ocorre o tráfego de células mononuclerares em direção ao pulmão é fundamental não só para um maior entendimento da patogênese da DPOC, mas para o desenvolvimento de terapêuticas adequadas. Com base nessas evidências tem sido proposto o estudo de moléculas capazes de bloquear de forma específica o recrutamento de células inflamatórias para o pulmão por meio de ação direta nos seus receptores.Unitermos: DPOC. Inflamação. Quimiocinas.células inflamatórias e seus mediadores na patogênese da dpoc

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Changes in elastic fibres in the small airways and alveoli in COPD

Cited by 136 publications

References 25 publications

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts

Effects of Pulmonary Rehabilitation on Lung Functions in Patients with COPD

Células inflamatórias e seus mediadores na patogênese da DPOC

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