Histological hallmarks and role of Slug/
            <scp>PIP</scp>
            axis in pulmonary hypertension secondary to pulmonary fibrosis

Ruffenach, Grégoire; Umar, Soban; Vaillancourt, Mylène; Hong, Jason; Cao, Nancy; Sarji, Shervin; Moazeni, Shayan; Cunningham, Christine M.; Ardehali, A.; Reddy, Srinivasa T.; Saggar, Rajan; Fishbein, Gregory A.; Eghbali, Mansoureh

doi:10.15252/emmm.201810061

Cited by 17 publications

(12 citation statements)

References 53 publications

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“…Targeting aberrant signaling of bioactive lipids can be a therapeutic strategy for COVID-19 [41,42]. We have shown that apoA-I mimetics bind [43] and remove [44] oxidized lipids from the circulation, thus reducing the oxidative stress that contributes to endothelial dysfunction, pulmonary hypertension and lung cancer in murine models of lung disease [11,[45][46][47]. Bioactive lipids may also disrupt epithelial cell tight junctions either directly [48] or through lipid raft disruption [49,50] or TNF-α signaling [51].…”

Section: Discussionmentioning

confidence: 99%

The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

et al. 2021

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An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates in vitro SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19.

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Section: Discussionmentioning

confidence: 99%

The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

et al. 2021

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“…153 In this relatively easy-to-handle animal model with many variations in terms of dosage and route of delivery, muscularization of pulmonary vessels accompanied with or without the presence of mild PH has been repeatedly described. [154][155][156][157] Since elevation of RVSP in bleomycin-challenged rodents is most often modest and occurs concomitantly with the appearance of fibrotic lesions, a 2-hit rat model by sequential exposure to bleomycin and MCT was recently developed to more adequately recapitulate group 3 PH. 156,157 As revealed by histological analyses, hydroxyproline assay, lung function testing, and right heart catheterization, the combination of these insults results in pronounced fibrosis associated with altered mechanical properties of the respiratory system and a robust PH phenotype, 156,157 making this model more appropriate to assess the impact of drugs on the development of PH in preexisting pulmonary fibrosis.…”

Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure

Boucherat

Agrawal

Lawrie

et al. 2022

Circulation Research

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Pulmonary hypertension (PH) describes heterogeneous population of patients with a mean pulmonary arterial pressure >20 mm Hg. Rarely, PH presents as a primary disorder but is more commonly part of a complex phenotype associated with comorbidities. Regardless of the cause, PH reduces life expectancy and impacts quality of life. The current clinical classification divides PH into 1 of 5 diagnostic groups to assign treatment. There are currently no pharmacological cures for any form of PH. Animal models are essential to help decipher the molecular mechanisms underlying the disease, to assign genotype-phenotype relationships to help identify new therapeutic targets, and for clinical translation to assess the mechanism of action and putative efficacy of new therapies. However, limitations inherent of all animal models of disease limit the ability of any single model to fully recapitulate complex human disease. Within the PH community, we are often critical of animal models due to the perceived low success upon clinical translation of new drugs. In this review, we describe the characteristics, advantages, and disadvantages of existing animal models developed to gain insight into the molecular and pathological mechanisms and test new therapeutics, focusing on adult forms of PH from groups 1 to 3. We also discuss areas of improvement for animal models with approaches combining several hits to better reflect the clinical situation and elevate their translational value.

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“…In PAH, the biological processes of PA-SMCs and PA-ECs are abnormal, characterized by increased proliferation and Expression of the microRNA-30 family in pulmonary arterial hypertension and the role of microRNA-30d-5p in the regulation of pulmonary arterial smooth muscle cell toxicity and apoptosis reduced apoptosis (9)(10)(11). miRNAs participate in the regulation of proliferation and apoptosis in numerous diseases.…”

Section: Introductionmentioning

confidence: 99%

Expression of the microRNA‑30 family in pulmonary arterial hypertension and the role of microRNA‑30d‑5p in the regulation of pulmonary arterial smooth muscle cell toxicity and apoptosis

Liu

et al. 2021

Exp Ther Med

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The biological processes of pulmonary artery vascular smooth muscle cells (PA-SMCs) and pulmonary artery endothelial cells in pulmonary arterial hypertension (PAH) are generally abnormal, with increased levels of proliferation and reduced levels of apoptosis. Although microRNAs (miRNAs/miRs) participate in a number of biological processes in a variety of diseases, such as tumors and infections, studies on the association between miRNAs and PAH are limited. In the present study, blood samples were collected from 6 patients with patent ductus arteriosus. The experimental group included 3 patients with severe PAH, while the control group included 3 patients without PAH. Microarray technology was used to detect the presence of any associated miRNAs. Moreover, a rat PAH model was established via left lung resection followed by monocrotaline injection, involving a total of 8 rats in the PAH group and 8 untreated rat in the control group. Reverse transcription-quantitative PCR was performed to verify the expression levels of the miR-30 family in the animal model. miR-30d-5p mimics and anti-miR-30d-5p were transfected into primary cultured PA-SMCs. Levels of cytotoxicity and cell apoptosis were examined, and Notch-3 expression levels were studied using western blotting. The results of the present study demonstrated that miR-30d-5p expression was downregulated in both patient blood and animal models of the PAH group compared with control groups. In primary cultured PA-SMCs, overexpression of miR-30d-5p attenuated the platelet-derived growth factor-induced toxicity of PA-SMCs, while knockdown of miR-30d-5p resulted in the increased toxicity of PA-SMCs compared with control group.The apoptosis rate of PA-SMCs increased with the overexpression of miR-30d-5p compared with control group. Moreover, the expression levels of Notch-3 in the miR-30d-5p group were significantly reduced compared with the anti-miR-30d-5p and miR-NC groups. In total, 10 circulating miRNAs that may be associated with PAH were discovered in the present study. Moreover, the expression of the miR-30 family was verified in animal models in vivo, and seven miRNAs in this family were discovered that may be associated with PAH. Additionally, miR-30d-5p was downregulated in both patients with PAH and animal models compared with control groups. Thus, the results of the present study demonstrated that the regulatory mechanism underlying PA-SMCs may be via the Notch-3 signaling pathway.

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Histological hallmarks and role of Slug/ PIP axis in pulmonary hypertension secondary to pulmonary fibrosis

Cited by 17 publications

References 53 publications

The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure

Expression of the microRNA‑30 family in pulmonary arterial hypertension and the role of microRNA‑30d‑5p in the regulation of pulmonary arterial smooth muscle cell toxicity and apoptosis

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