Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease

Khedoe, P. Padmini S.J.; Rensen, Patrick C.N.; Berbée, Jimmy F.P.; Hiemstra, Pieter S.

doi:10.1152/ajplung.00013.2016

Cited by 9 publications

(9 citation statements)

References 260 publications

(207 reference statements)

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“…Furthermore ApoE −/− mice fed a western diet had significantly higher BALF TNF-α, IL-4, IL-6, IL-17, and IFN-γ compared to normal chow fed ApoE −/− mice [ 29 ]. Additionally, recent reviews contain excellent discussions on the emergence of this model in CVD/COPD comorbidity studies [ 4 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke

Florence

Krupa

Booshehri

et al. 2018

IJMS

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Chronic obstructive pulmonary disease (COPD) is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression of this disease remains unknown. Our laboratory has demonstrated that Bruton’s tyrosine kinase (Btk) is a critical regulator of pro-inflammatory processes in the lungs and that Btk controls expression of matrix metalloproteinase-9 (MMP-9) in the alveolar compartment. For this study apolipoprotein E null (ApoE−/−) mice were exposed to SHS to facilitate study in a COPD/atherosclerosis comorbidity model. We applied two types of treatments, animals received either a pharmacological inhibitor of Btk or MMP-9 specific siRNA to minimize MMP-9 expression in endothelial cells or neutrophils. We have shown that these treatments had a protective effect in the lung. We have noted a decrease in alveolar changes related to SHS induced inflammation in treated animals. In summary, we are presenting a novel concept in the field of COPD, i.e., that Btk may be a new drug target for this disease. Moreover, cell specific targeting of MMP-9 may also benefit patients affected by this disease.

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Section: Discussionmentioning

confidence: 99%

Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke

Florence

Krupa

Booshehri

et al. 2018

IJMS

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“…Oxidative stress (OS) contributes to a wide range of human diseases, such as neurodegeneration [ 1 – 4 ], cancer [ 5 – 7 ], cardiac conditions such as hypertension and atherosclerosis [ 8 – 11 ], and cell death associated with ischemia/reperfusion injuries [ 12 , 13 ]. It is also a common mechanism leading to cellular damage caused by chemical exposure in humans [ 14 – 16 ] and wildlife species [ 17 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae

Mills

Gallagher

2017

PLoS ONE

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Chemical-induced oxidative stress and the biochemical pathways that protect against oxidative damage are of particular interest in the field of toxicology. To rapidly identify oxidative stress-responsive gene expression changes in zebrafish, we developed a targeted panel of antioxidant genes using the Affymetrix QuantiGene Plex (QGP) platform. The genes contained in our panel include eight putative Nrf2 (Nfe2l2a)-dependent antioxidant genes (hmox1a, gstp1, gclc, nqo1, prdx1, gpx1a, sod1, sod2), a stress response gene (hsp70), an inducible DNA damage repair gene (gadd45bb), and three reference genes (actb1, gapdh, hprt1). We tested this platform on larval zebrafish exposed to tert-butyl hydroperoxide (tBHP) and cadmium (Cd), two model oxidative stressors with different modes of action, and compared our results with those obtained using the more common quantitative PCR (qPCR) method. Both methods showed that exposure to tBHP and Cd induced expression of prdx1, gstp1, and hmox1a (2- to 12-fold increase via QGP), indicative of an activated Nrf2 response in larval zebrafish. Both compounds also elicited a general stress response as reflected by elevation of hsp70 and gadd45bb, with Cd being the more potent inducer. Transient changes were observed in sod2 and gpx1a expression, whereas nqo1, an Nrf2-responsive gene in mammalian cells, was minimally affected by either tBHP or Cd chemical exposures. Developmental expression analysis of the target genes by QGP revealed marked upregulation of sod2 between 0-96hpf, and to a lesser extent, of sod1 and gstp1. Once optimized, QGP analysis of these experiments was accomplished more rapidly, using far less tissue, and at lower total costs than qPCR analysis. In summary, the QGP platform as applied to higher-throughput zebrafish studies provides a reasonable cost-effective alternative to qPCR or more comprehensive transcriptomics approaches to rapidly assess the potential for chemicals to elicit oxidative stress as a mechanism of chemical toxicity.

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“…Aqueous extracts of CS as well as intratracheal or intranasal administration of proteases (elastase or papain) (for review see [19] can also be used to study emphysema and the effects of COPD-associated systemic manifestations.…”

Section: Animal Models Of Copd Other Than Cs Exposurementioning

confidence: 99%

“…Furthermore, other models in which mice are treated with antibodies against endothelial cells or the receptor of vascular endothelial growth factor (VEGF) have been also used to induce alveolar septal apoptosis, oxidative stress, and in the end emphysema in their lungs [19][20][21].…”

Section: Animal Models Of Copd Other Than Cs Exposurementioning

confidence: 99%

COPD: preclinical models and emerging therapeutic targets

Barreiro

Wang

Tang

2019

Expert Opinion on Therapeutic Targets

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Introduction: Chronic obstructive pulmonary disease (COPD) is a common disease and a leading cause of morbidity and mortality worldwide. Preclinical models of COPD have been developed lately. In those models, COPD/emphysema has been commonly induced using different toxic agents such as elastase, proteolytic enzymes, and chronic exposure to cigarette smoke (CS). Areas Covered: The most relevant features of preclinical models of COPD, namely chronic exposure to CS and other agents (proteases and microorganisms), cardiovascular effects, surfactant protein-D, airway remodeling and inflammation, lung regeneration potential, and mesenchymal stromal cell therapy are being described in the review below. The most relevant publications on the topic of interest were selected from PubMed and used to write this review. Expert opinion: Preclinical models of COPD are key elements to understand the underlying biology and pathophysiology of the disease with the aim to design of therapeutic targets. Increased knowledge on the most relevant biological insights will help design therapeutic targets for the treatment of patients with COPD. This will enable health caregivers and doctors to better treat their patients, in which a more holistic approach will be used. This will benefit the patients and the society as the use of resources should be significantly diminished.

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Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease

Cited by 9 publications

References 260 publications

Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke

Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke

A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae

COPD: preclinical models and emerging therapeutic targets

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