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Biomedicines
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Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and...
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Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and Inflammation

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 4783

Special Issue Editor

Dr. Lan Zhao

E-Mail Website
Guest Editor
1. Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
2. Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University, Stanford, CA 94305, USA
Interests: pulmonary hypertension; microbiome; metabolomics; non-coding RNAs; big data; meta-analysis; animal models

Special Issue Information

Dear Colleagues,

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by vascular remodeling and dysfunction in the lungs. Apart from the BMPR2 mutations responsible for a subset of PAH, various other genetic and environmental factors contribute to the pathogenesis of PAH, including sex, drugs and microbiome. Emerging data suggest that perturbations in gut and respiratory microbial communities could result in chronic hypoxia, inflammation, and pulmonary vascular injury. Whether microbial changes are the cause or the consequence of vascular inflammation and injury in PAH remains to be determined.

Recent culture-free microbiome studies based on high-throughput sequencing and functional metabolomics have and will continue to provide insights into the relationship between microbiome and PAH. Moreover, specific microbial biomarkers have been shown to have promising diagnostic and therapeutic benefits in patients with PAH. The Special Issue invites contributions investigating the molecular mechanisms involving the microbiome in PAH vascular remodeling and disease progression, as well as respiratory and cardiac dysfunctions associated with chronic hypoxia and inflammation. Both original experimental and clinical research and review papers are welcome.

Dr. Lan Zhao
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pulmonary arterial hypertension
  • gut microbiome
  • respiratory microbiome
  • chronic hypoxia
  • inflammation
  • vascular injury
  • metabolomics

Published Papers (4 papers)

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Research

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21 pages, 15708 KiB  
Article
Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets
by Yilu Feng, Zaixin Yu, Mi Tang, Jiang Li, Baohua Peng, Mukamengjiang Juaiti, Yiyang Tang, Benhui Liang, Mingqi Ouyang, Qingqing Liu and Jie Song
Biomedicines 2024, 12(2), 364; https://doi.org/10.3390/biomedicines12020364 - 04 Feb 2024
Viewed by 857
Abstract
N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of [...] Read more.
N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein–protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future. Full article
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and Inflammation)
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Review

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17 pages, 558 KiB  
Review
Pulmonary Hypertension and the Gut Microbiome
by Thomas Mason, Bhashkar Mukherjee and Philip Marino
Biomedicines 2024, 12(1), 169; https://doi.org/10.3390/biomedicines12010169 - 12 Jan 2024
Viewed by 798
Abstract
The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic [...] Read more.
The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic hypertension, atherosclerosis). Pulmonary hypertension (PH) is a condition characterised by progressive remodelling and vasoconstriction of the pulmonary circulation, ultimately leading to right ventricular failure and premature mortality if untreated. Initial studies have suggested a possible association between dysbiosis of the microbiome and the development of PH. The aim of this article is to review the current experimental and clinical data with respect to the potential interaction between the gut microbiome and the pathophysiology of pulmonary hypertension. It will also highlight possible new therapeutic targets that may provide future therapies. Full article
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and Inflammation)
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16 pages, 1308 KiB  
Review
Chronic Thromboembolic Pulmonary Hypertension: A Review of the Multifaceted Pathobiology
by Hakim Ghani and Joanna Pepke-Zaba
Biomedicines 2024, 12(1), 46; https://doi.org/10.3390/biomedicines12010046 - 24 Dec 2023
Viewed by 1047
Abstract
Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can [...] Read more.
Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can lead to right heart failure and death. The pathobiology of CTEPH has been challenging to unravel due to its rarity, possible interference of results with anticoagulation, difficulty in selecting the most relevant study time point in relation to presentation with acute pulmonary embolism (PE), and lack of animal models. In this article, we review the most relevant multifaceted cross-talking pathogenic mechanisms and advances in understanding the pathobiology in CTEPH, as well as its challenges and future direction. There appears to be a genetic background affecting the relevant pathological pathways. This includes genetic associations with dysfibrinogenemia resulting in fibrinolysis resistance, defective angiogenesis affecting thrombus resolution, and inflammatory mediators driving chronic inflammation in CTEPH. However, these are not necessarily specific to CTEPH and some of the pathways are also described in acute PE or deep vein thrombosis. In addition, there is a complex interplay between angiogenic and inflammatory mediators driving thrombus non-resolution, endothelial dysfunction, and vascular remodeling. Furthermore, there are data to suggest that infection, the microbiome, circulating microparticles, and the plasma metabolome are contributing to the pathobiology of CTEPH. Full article
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and Inflammation)
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13 pages, 1337 KiB  
Review
A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension
by Jamie L. Archambault and Cassidy A. Delaney
Biomedicines 2023, 11(11), 3049; https://doi.org/10.3390/biomedicines11113049 - 14 Nov 2023
Viewed by 1093
Abstract
Serotonin (5-HT) is a bioamine that has been implicated in the pathogenesis of pulmonary hypertension (PH). The lung serves as an important site of 5-HT synthesis, uptake, and metabolism with signaling primarily regulated by tryptophan hydroxylase (TPH), the 5-HT transporter (SERT), and numerous [...] Read more.
Serotonin (5-HT) is a bioamine that has been implicated in the pathogenesis of pulmonary hypertension (PH). The lung serves as an important site of 5-HT synthesis, uptake, and metabolism with signaling primarily regulated by tryptophan hydroxylase (TPH), the 5-HT transporter (SERT), and numerous unique 5-HT receptors. The 5-HT hypothesis of PH was first proposed in the 1960s and, since that time, preclinical and clinical studies have worked to elucidate the role of 5-HT in adult PH. Over the past several decades, accumulating evidence from both clinical and preclinical studies has suggested that the 5-HT signaling pathway may play an important role in neonatal cardiopulmonary transition and the development of PH in newborns. The expression of TPH, SERT, and the 5-HT receptors is developmentally regulated, with alterations resulting in pulmonary vasoconstriction and pulmonary vascular remodeling. However, much remains unknown about the role of 5-HT in the developing and newborn lung. The purpose of this review is to discuss the implications of 5-HT on fetal and neonatal pulmonary circulation and summarize the existing preclinical and clinical literature on 5-HT in neonatal PH. Full article
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension: Focus on the Microbiome and Inflammation)
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