Hypoxia-Inducible Factor-1: A Potential Target to Treat Acute Lung Injury

Liu, Yang; Du, Xiang; Zhang, Hengcheng; Yao, Hanlin; Wang, Yanfeng

doi:10.1155/2020/8871476

Cited by 46 publications

(29 citation statements)

References 165 publications

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“…Acute lung injury (ALI) and its worse form, acute respiratory distress syndrome (ARDS) consist of a set of pathological lung modifications that occur from pulmonary destructive events, such as pneumonia, sepsis, pulmonary trauma, viral infections and various other situations or diseases (116)(117)(118). Such phenomena deteriorate the vascular endothelium and the alveolar epithelium (119) resulting in loss of function of the corresponding cells due to excessive inflammation, hypoxemia and eventually respiratory failure (120,121). Both ALI and ARDS, due to the severe nature of their manifestations, are characterized by high mortality rates, despite the available treatment options that aim to optimize the diseases' outcome (116,122).…”

Section: Acute Lung Injury Acute Respiratory Distress Syndrome and Ace I/d Polymorphismmentioning

confidence: 99%

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity and mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation and blood pressure, but also contributing to normal pulmonary function and development. Angiotensin-converting enzyme (ACE) and its homologous angiotensin-converting enzyme 2 (ACE2) are considered to be amongst the main RAS regulators and are highly expressed in the pulmonary vascular endothelium. This review discusses the impact of ACE and ACE2 functional gene polymorphisms on seven major pulmonary diseases, in terms of predisposition, course, and outcome, revealing their potential utility as both genetic markers and biomarkers. The discussed conditions include chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), lung cancer and pulmonary sarcoidosis (PS), as well as SARS-CoV-2 viral infection and COVID-19 disease.Chronic respiratory diseases (CRDs) have been among the leading causes of morbidity and mortality around the globe for the last two decades (1-3). Their constantly increasing rates of occurrence may vary both between the genders, but also between different regions and socio-economic backgrounds (4). Nevertheless, the common denominator includes the deterioration of patients' quality of life that can often lead to several years of disability. The main CRDs are chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma and lung cancer, with COPD alone being the third leading cause of death worldwide, as reported in 2010 (1,5,6).On the other hand, acute lung diseases with an infectional etiology, pose a significant threat not only to lung health but also to human life (7). A recent great example is the 2019 outbreak of the novel coronavirus strain SARS-CoV-2 in China, causing the extremely infectious disease COVID-19, that led to a global pandemic and to millions of deaths, mainly due to severe respiratory complications (8, 9). So far, therapeutic approaches are mainly symptomatic, while knowledge on the exact pathogenetic mechanisms for complex lung-diseases remains limited. Consequently, prevention is predominantly based on general lifestyle guidelines, whereas the establishment of a priori personalized preventive measures, according to an individual's genetic predisposition, is still in its infancy (1, 5). Nevertheless, there are important known genetic markers that may be utilized for their predictive value.The renin-angiotensin system (RAS), in addition to its great importance for the overall homeostasis of the body, through the regulation of blood pressure and electrolyte balance, has a strong tissue-specific expression in the respiratory tract and functions both autonomously and 13 This article is freely accessible online.

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Section: Acute Lung Injury Acute Respiratory Distress Syndrome and Ace I/d Polymorphismmentioning

confidence: 99%

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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“…Upregulated TF HIF1A is a critical indicator in response to cellular hypoxia conditions. The inflammation role of TF HIF1α has also been investigated in ARDS caused by different agents, suggesting that silencing HIF1 depends on NFκB and could be a possible strategy for preventing the aggravation of inflammation in ARDS [ 46 , 47 , 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Ting

Chen

2022

IJMS

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The coronavirus disease 2019 (COVID-19) epidemic is currently raging around the world at a rapid speed. Among COVID-19 patients, SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) is the main contribution to the high ratio of morbidity and mortality. However, clinical manifestations between SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS are quite common, and their therapeutic treatments are limited because the intricated pathophysiology having been not fully understood. In this study, to investigate the pathogenic mechanism of SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS, first, we constructed a candidate host-pathogen interspecies genome-wide genetic and epigenetic network (HPI-GWGEN) via database mining. With the help of host-pathogen RNA sequencing (RNA-Seq) data, real HPI-GWGEN of COVID-19-associated ARDS and non-viral ARDS were obtained by system modeling, system identification, and Akaike information criterion (AIC) model order selection method to delete the false positives in candidate HPI-GWGEN. For the convenience of mitigation, the principal network projection (PNP) approach is utilized to extract core HPI-GWGEN, and then the corresponding core signaling pathways of COVID-19-associated ARDS and non-viral ARDS are annotated via their core HPI-GWGEN by KEGG pathways. In order to design multiple-molecule drugs of COVID-19-associated ARDS and non-viral ARDS, we identified essential biomarkers as drug targets of pathogenesis by comparing the core signal pathways between COVID-19-associated ARDS and non-viral ARDS. The deep neural network of the drug–target interaction (DNN-DTI) model could be trained by drug–target interaction databases in advance to predict candidate drugs for the identified biomarkers. We further narrowed down these predicted drug candidates to repurpose potential multiple-molecule drugs by the filters of drug design specifications, including regulation ability, sensitivity, excretion, toxicity, and drug-likeness. Taken together, we not only enlighten the etiologic mechanisms under COVID-19-associated ARDS and non-viral ARDS but also provide novel therapeutic options for COVID-19-associated ARDS and non-viral ARDS.

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“…are known to indirectly abrogate HIF-1α stability and signalling. Some works have suggested repurposing them to manage inflammation in the lung ( Liu et al, 2020 ). A recent work suggests making PHD2 inhibitors a part of COVID-19 treatment regimen to increase erythropoiesis and reduce ferroptosis ( Poloznikov et al, 2021 ).…”

Section: Therapeutic Interventionmentioning

confidence: 99%

Interplay between hypoxia and inflammation contributes to the progression and severity of respiratory viral diseases

Bhattacharya

Agarwal

Shrimali

et al. 2021

Molecular Aspects of Medicine

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History of pandemics is dominated by viral infections and specifically respiratory viral diseases like influenza and COVID-19. Lower respiratory tract infection is the fourth leading cause of death worldwide. Crosstalk between resultant inflammation and hypoxic microenvironment may impair ventilatory response of lungs. This reduces arterial partial pressure of oxygen, termed as hypoxemia, which is observed in a section of patients with respiratory virus infections including SARS-CoV-2 (COVID-19). In this review, we describe the interplay between inflammation and hypoxic microenvironment in respiratory viral infection and its contribution to disease pathogenesis.

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Hypoxia-Inducible Factor-1: A Potential Target to Treat Acute Lung Injury

Cited by 46 publications

References 165 publications

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Interplay between hypoxia and inflammation contributes to the progression and severity of respiratory viral diseases

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